Advertisement

Bipolar Disorder Research and New Medicine Trials

Clinical Trial of Pramipexole in Bipolar Depression

This study is currently recruiting patients.

Sponsored by: National Institute of Mental Health (NIMH)
Information provided by: Warren G Magnuson Clinical Center (CC)

Purpose

The purpose of this study is to examine the safety and effectiveness of the drug pramipexole given in combination with lithium or divalproex for the short-term treatment of acute depression in patients with bipolar disorder.

Bipolar disorder is a severe, chronic, and often life-threatening illness. Treatments for acute unipolar depression have been extensively researched. However, despite the availability of a wide range of antidepressant drugs, a significant proportion of depressed patients fail to respond to first-line antidepressant treatment. Novel and improved therapeutics for bipolar depression are needed. This study will evaluate the antidepressant properties of pramipexole.

This study will be conducted in three phases. Phase 1 is a 14-day washout period in which participants will be tapered off all their psychiatric medicines except divalproex or lithium. Participants will also be asked to adhere to a low caffeine and low monoamine diet. During Phase 2, participants will be randomly assigned to receive either pramipexole or placebo (an inactive pill) for 6 weeks. Participants who respond to treatment will be given either open-label pramipexole or another clinical treatment.

Participants will be screened with a medical history, physical examination, electrocardiogram (EKG), blood and urine tests, and a psychiatric evaluation. Women of childbearing potential will have a pregnancy test. Participants will have a physical exam and EKG at study entry and study completion. Blood will be drawn at various times throughout the study. Pulse and blood pressure measurements will be taken daily. Weekly interviews will be conducted. Participants and a control group of healthy volunteers will undergo positron emission tomography (PET) and magnetic resonance imaging (MRI) scans of the brain.

Condition Phase
Bipolar Disorder
Phase II

MedlinePlus related topics:  Bipolar Disorder

Study Type: Interventional
Study Design: Treatment, Safety/Efficacy

Official Title: An Investigation of the Antidepressant Efficacy of a Dopamine Agonist with Neurotrophic Properties in Bipolar Disorder

Further Study Details: 

Expected Total Enrollment:  120

Study start: October 22, 2001

Bipolar affective disorder (BPD, manic-depressive illness) is a common, severe, chronic and often life-threatening illness. Increasingly, it is being recognized that it is the depressive phase of the illness, which contributes much of the morbidity and mortality. Impairment in physical and social functioning resulting from depression can be just as severe as other chronic medical illnesses. Suicide is the cause of death in 10-20% of individuals with either bipolar or recurrent depressive disorders.

The treatments for acute unipolar depression have been extensively researched. However, despite the availability of a wide range of antidepressant drugs, clinical trials indicate that 30% to 40% of (unipolar) depressed patients fail to respond to first-line antidepressant treatment, despite adequate dosage, duration, and compliance. Very few studies have examined the efficacy of somatic treatments for the acute phase of bipolar depression. Thus, there is a clear need to develop novel and improved therapeutics for bipolar depression. A deficiency of dopamine systems stands as a prime candidate for involvement in the pathophysiology of depression.

Preliminary studies suggest that pramipexole (Mirapex), a dopaminergic-agent that is FDA-approved for Parkinson's Disease, may have antidepressant properties in unipolar and bipolar patients as well as neurotrophic properties. In this study, we propose to investigate the potential efficacy of pramipexole, which enhances dopaminergic throughput via D2 and D3 receptors, and exerts robust neurotrophic effects via direct intracellular mechanisms.

This is a 6-week randomized double-blind, placebo-controlled add-on study that will examine the efficacy of pramipexole in acutely depressed Bipolar II patients.

This study has three phases. The first phase is the washout phase that will last for 14 days. The second phase is a 6-week double-blind acute phase in which the efficacy and tolerability of adjunctive pramipexole and placebo are compared. Patients who complete the 6-week double-blind phase will receive either open-label pramipexole or clinical treatment. Acute efficacy will be determined by demonstrating a greater response rate using specified criteria.

Patients, ages 18 to 60, with a diagnosis of Bipolar II disorder, depressed (without psychotic features), will be randomized to double-blind treatment to receive either pramipexole (0.375-4.5 mg/day) or placebo in combination with a mood stabilizer for a period of 6 weeks. Following this acute period, the patients will receive either open-label pramipexole or treatment as clinically indicated. Approximately 100 patients with acute Bipolar II depression will be enrolled in the study. Imaging and pharmacokinetic studies will be obtained during the study.

Eligibility

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA:
Male or female subjects, 18 to 60 years of age.
Female subjects of childbearing potential must be using a medically accepted means of contraception.
Each subject must understand the nature of the study and must sign an informed consent document.
Subjects must fulfill the criteria for Bipolar II disorder depressed without psychotic features as defined in DSM-IV (296.89) based on clinical assessment and confirmed by structured diagnostic interview SCID-P.
Subjects must have an initial score at Visit 1 and Visit 2 of at least 20 on the MADRS.
Subjects must have experienced, in the opinion of the investigator, at least two previous hypomanic and two major depressive episodes as defined in DSM-IV.
Subjects must have failed to respond in the past to an adequate dose and duration of at least one antidepressant (SSRI, bupropion, or venlafaxine) during an episode of major depression.
Subjects must have been receiving treatment with VPA or lithium (valproate 50-125 micro grams/ml or lithium 0.6-1.2 mEq/L) for at least 4 weeks prior to Visit 1. At least two blood levels of lithium and VPA must be within therapeutic range (each at least 1 week apart) prior to Visit 1.
Current major depressive episode no more than 24 months.
EXCLUSION CRITERIA:
Subjects not taking lithium or valproate by the time of screening.
Presence of psychotic features
Participating in a clinical trial of another investigational drug within 1 month prior to study entry (Visit 1).
Female subjects who are either pregnant or nursing.
Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
Subjects with uncorrected hypothyroidism or hyperthyroidism.
Subjects with one or more seizures without a clear and resolved etiology.
Documented history of hypersensitivity or intolerance to pramipexole
DSM-IV substance abuse (except nicotine and caffeine) within the past 90 days and substance dependence within the past 5 years.
Subjects with a DSM-IV rapid cycling course of illness in the past 12-months.
Treatment with an injectable depot neuroleptic within less than one dosing interval prior to Visit 2.
Treatment with a reversible MAOI, guanethidine, or guanadrel within 1 week prior to Visit 2.
Treatment with fluoxetine within 8 weeks prior to Visit 2.
Treatment with any other concomitant medication (Appendix B) 1 day prior to Visit 2.
Treatment with clozapine or ECT within 3 months prior to Visit 2.
Current diagnosis of schizophrenia or other psychotic disorder as defined in the DSM-IV.
Judged clinically to be at serious suicidal risk.
Patients will not be allowed to receive structured psychotherapy during the trial.

Location and Contact Information


Maryland
      National Institute of Mental Health (NIMH), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting
Patient Recruitment and Public Liaison Office  1-800-411-1222    prpl@mail.cc.nih.gov 
TTY  1-866-411-1010 

More Information

Detailed Web Page

Publications

Amsterdam JD, Garcia-Espana F, Fawcett J, Quitkin FM, Reimherr FW, Rosenbaum JF, Schweizer E, Beasley C. Efficacy and safety of fluoxetine in treating bipolar II major depressive episode. J Clin Psychopharmacol. 1998 Dec;18(6):435-40.

Amsterdam JD, Garcia-Espana F. Venlafaxine monotherapy in women with bipolar II and unipolar major depression. J Affect Disord. 2000 Sep;59(3):225-9.

Amsterdam JD, Berwish NJ. High dose tranylcypromine therapy for refractory depression. Pharmacopsychiatry. 1989 Jan;22(1):21-5.

Study ID Numbers:  020018; 02-M-0018
Record last reviewed:  October 22, 2003
Last Updated:  October 22, 2003
Record first received:  October 24, 2001
ClinicalTrials.gov Identifier:  NCT00025792
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-27

Clinical Trial of Mifepristone for Bipolar Depression

This study is currently recruiting patients.

Sponsored by: National Institute of Mental Health (NIMH)
Information provided by: Warren G Magnuson Clinical Center (CC)

Purpose

The purpose of this study is to determine the effectiveness of the drug mifepristone in treating patients with bipolar depression who are taking mood stabilizers. This study will also investigate how mifepristone and certain hormones cause changes in mood, thinking, and memory in some patients with bipolar depression.

Bipolar depression is a severe illness with high rates of psychiatric comorbidity and increased mortality related to suicide and medical illness. Hypothalamic pituitary axis (HPA) hyperactivity is found in patients with bipolar depression. These patients also have cognitive difficulties and endocrine disturbances that may contribute to such dysfunction. Antiglucocorticoid therapies are novel treatments for mood disorders. Mifepristone, a glucocorticoid receptor antagonist, may have antidepressant and positive cognitive effects in patients with mood disorders. This study will examine the effects of mifepristone in combination with mood stabilizers in patients with severe bipolar depression.

Participants with bipolar depression will be admitted to the Clinical Center for 3 to 4 weeks. They will be tapered off all psychiatric medications except Depakote (valproate) and/or lithium. Participants will then begin taking a placebo (an inactive pill) and initiate baseline testing in which they will undergo a magnetic resonance imaging (MRI) scan of the brain. At the end of the baseline studies, participants will be randomly assigned to receive mifepristone or to continue taking a placebo. After 1 week, participants taking mifepristone will be switched to placebo; those taking a placebo will be switched to mifepristone. The crossover treatment will continue for 1 week. Those who respond well to treatment and do not require additional antidepressant medications will remain in the study for up to 16 weeks as outpatients. All others will have further short-term treatment and arrangements will be made for long-term treatment.

A comparison group of healthy volunteers will be admitted to the Clinical Center for two overnight stays for various procedures. Volunteers may be asked to return to the clinic for further testing.

Condition Treatment or Intervention Phase
Bipolar Disorder
 Drug: Mifepristone
Phase II

MedlinePlus related topics:  Bipolar Disorder

Study Type: Interventional
Study Design: Treatment, Safety/Efficacy

Official Title: Antiglucocorticoid Therapy in Bipolar Depression with Mifepristone (RU486)

Further Study Details: 

Expected Total Enrollment:  110

Study start: August 7, 2002

Bipolar Depression is a severe illness with high rates of psychiatric comorbidity and increased mortality related to suicide and medical illness. Hypothalamic pituitary axis (HPA) hyperactivity are found in bipolar disorder related to depression and mixed states. Patients with bipolar disorder also have cognitive difficulties and endocrine disturbances and may contribute to such dysfunction. Antiglucorticoid therapies are novel treatments of mood disorder. Preliminary data in psychotic depression suggesting that mifepristone (RU 486), a glucocorticoid receptor antagonist, has antidepressant and salutary cognitive effects in a matter of days. In this study we examine the effects of mifepristone in severe bipolar depression in a parallel, double blind placebo controlled experiment. Bipolar subjects maintained on lithium, valproate, or both after washout of prior antidepressants will have a detailed neuroendocrine assessment. Patients (n=75) will receive eight days of mifepristone versus placebo after which patients are blindly crossed over to the opposite arm. Patients and a group of matched controls (n=35) will be compared with neuroendocrine, cognitive, and neurophysiologic testing to fully characterize their phenotype and explore biomarkers of response. It is hypothesized that stigmata of HPA axis hyperactivity and cognitive impairment will be predictive of response to antiglucocorticoid therapy with mifepristone.

Eligibility

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA FOR BIPOLAR PATIENTS:
Patients must meet the following inclusion criteria in order to participate in the study:
a) Male or female inpatients in need of treatment for severe bipolar depression.
b) 18-75 years of age.
c) Women of childbearing potential must be using an adequate form of contraception as defined by one of the following: 1) a barrier method and 2) oral contraceptives plus a barrier method (women who are on an OCP will be kept on it others must agree to use only a barrier method).
d) DSM-IV diagnosis of bipolar depression I/II, severe, with or without psychotic features.
e) A current major depressive episode of at least 6 weeks' duration.
f) Score of greater than or equal to 28 on the first 24-item HAM-D at the prestudy visit and at the first baseline phase visit.
g) Score of 20 or greater on the HAM-D (24) at the end of the baseline period(s) (i.e., at randomization no more than 20% less than entry enrollment criteria).
h) Score of greater than or equal to 4 on the CGI-BP scale at the prestudy and first visit and end of baseline phase.
i) Judged to be in good physical health on the basis of medical history, physical examination, and laboratory screening.
j) Able to understand procedures and agree to participate in the study by giving written informed consent.
k) On lithium and/or valproate for at least 4 weeks (2 levels 1 wk apart).
l) However patients not on a mood stabilizer can have this started as an outpatient or inpatient for 4 weeks as discussed above.
m) Able to come off of prior drugs and PRN zolpidem and lorazepam by start of baseline.
EXCLUSION CRITERIA FOR BIPOLAR PATIENTS:
Patients will be excluded from the study if they meet any of the following criteria:
a) Women who are pregnant, intending to become pregnant in the next month or breast-feeding.
b) Treatment with any of the following therapies within the specified interval prior to baseline: Fluoxetine - 4 weeks; Investigational compounds - 4 weeks; MAOIs - 1 week; Other antidepressants - 1 week.
c) Contraindication or history of hypersensitivity to mifepristone as well as cortisol, and CRH.
d) Clinically significant organ system disease where mifepristone would be contraindicated or interfere with medical treatment.
e) Have evidence of any disorder that represents a contraindication to the use of mifepristone (such as adrenal disease or a condition requiring chronic corticosteroid administration).
f) History of Addison's Disease, Cushing's Disease, insulin dependent diabetes, or other uncompensated endocrine conditions.
g) Evidence of infection, severe liver, respiratory, or renal disease.
h) Have clinically significant cardiovascular disease, e.g., angina, valve disease, arrhythmia, cardiac failure.
i) Anemia (hemoglobin less than 10 g/dL or hematocrit less than 30%).
j) Have a known clotting defect or are receiving anticoagulants.
k) Rapid cycling in the last year (defined as greater than 6 episodes).
l) History of porphyries.
m) Clinically significant abnormalities in physical exam, ECG, or laboratory assessments.
n) History of any disease which, in the investigator's opinion may confound the results of the study or pose an additional risk, including but not limited to, history of organic mental disorder, seizures, or mental retardation.
o) Substance dependence that is not in sustained full remission (DSM-IV definition).
p) Other principal psychiatric diagnosis judged by the investigator to dominate the clinical presentation. In particular, patients with depressive symptoms more than 2 years in duration should be carefully evaluated to determine whether another psychiatric diagnosis exists which could interfere with efficacy and safety measurements.
q) History of nonresponse to greater than four trials of antidepressants for the current episode (not including mood stabilizers) will exclude subjects.
INCLUSION CRITERIA FOR NORMAL CONTROLS:
a) SCID-NP-no psychiatric diagnosis lifetime.
b) Ages 18-75.
c) Medically and psychiatrically healthy by history and no disallowed medications for 2 weeks, and agrees to no alcohol use for 1 week baseline period of study.
d) No history of mood or anxiety disorder in first-degree relatives.
e) Women of childbearing potential must be using adequate form of contraception as defined by one of the following: 1) a barrier method and 2) oral contraceptives plus a barrier method.
EXCLUSION CRITERIA FOR NORMAL CONTROLS:
a) Known hypersensitivity to CRH, hydrocortisone, metyrapone, or mifepristone.
b) Women who are pregnant or breast-feeding.
c) Clinically significant organ system disease where mifepristone would be contraindicated or interfere with medical treatment.
d) History of prophyrias.

Location and Contact Information


Maryland
      National Institute of Mental Health (NIMH), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting
Patient Recruitment and Public Liaison Office  1-800-411-1222    prpl@mail.cc.nih.gov 
TTY  1-866-411-1010 

More Information

Detailed Web Page

Publications

Murphy BE. Treatment of major depression with steroid suppressive drugs. J Steroid Biochem Mol Biol. 1991 Aug;39(2):239-44.

Murphy BE. Antiglucocorticoid therapies in major depression: a review. Psychoneuroendocrinology. 1997;22 Suppl 1:S125-32. Review.

Sapolsky RM. Stress, Glucocorticoids, and Damage to the Nervous System: The Current State of Confusion. Stress. 1996 Jul;1(1):1-19.

Study ID Numbers:  020251; 02-M-0251
Record last reviewed:  June 11, 2004
Last Updated:  June 11, 2004
Record first received:  August 9, 2002
ClinicalTrials.gov Identifier:  NCT00043654
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-27

Clinical Trial of Felbamate for Treatment-Resistant Bipolar Depression

This study is currently recruiting patients.

Sponsored by: National Institute of Mental Health (NIMH)
Information provided by: Warren G Magnuson Clinical Center (CC)

Purpose

The purpose of this study is to evaluate the safety and effectiveness of the drug felbamate for treating depression in patients with bipolar disorder that has not responded to standard treatments.

Bipolar disorder is a severe, chronic, and often life-threatening illness. Despite the availability of a wide range of antidepressant drugs, a proportion of patients fail to respond to first-line antidepressant treatment despite adequate dosage, duration, and compliance. Studies suggest that the glutamatergic system may play a role in the pathophysiology and treatment of depression. Felbamate and other agents which reduce glutamatergic neurotransmission may represent a novel class of antidepressants.

Participants in this study will be admitted to the Clinical Center for up to 10 weeks. At study entry, participants will have a 7-day washout period in which they will be tapered off all psychiatric medications, with the possible exception of lithium, and will be given a placebo (an inactive pill). After the washout period, participants will be randomly assigned to receive either felbamate or placebo for 8 weeks. Participants whose depression symptoms worsen by more than 30% or those for whom study continuation is considered potentially harmful will be taken off the study and offered open-label treatment. Participants who received felbamate and responded well to treatment will have the option of continuing treatment.

Condition Phase
Bipolar Disorder
Phase II

MedlinePlus related topics:  Bipolar Disorder

Study Type: Interventional
Study Design: Treatment, Safety/Efficacy

Official Title: A Double-Blind Randomized Placebo-Controlled Trial of Felbamate in Treatment Resistant Bipolar Depression

Further Study Details: 

Expected Total Enrollment:  52

Study start: April 18, 2002

Bipolar affective disorder (BPD, manic-depressive illness) is a common, severe, chronic and often life-threatening illness. Increasingly, it is being recognized that it is the depressive phase of the illness, which contributes much of the morbidity and mortality. Impairment in physical and social functioning resulting from depression can be just as severe as other chronic medical illnesses. Suicide is the cause of death in 10-20% of individuals with either bipolar or recurrent depressive disorders.

The treatments for acute unipolar depression have extensively researched. However, despite the availability of a wide range of antidepressant drugs, clinical trials indicate that 30% to 40% of depressed patients fail to respond to first-line antidepressant treatment, despite adequate dosage, duration, and compliance. Very few studies have examined the efficacy of somatic treatments for the acute phase of bipolar depression. Thus, there is a clear need to develop novel and improved therapeutics for bipolar depression. Recent preclinical studies suggest that antidepressants may exert delayed indirect effects on the glutamatergic system. Furthermore, a growing body of data suggests that mood disorders are associated with regional volumetric reductions, and cell loss and atrophy. It is noteworthy that lamotrigine reduces glutamatergic neurotransmission, has antidepressant effects in bipolar depression, and a pilot study has suggested that NMDA antagonists may have antidepressant effects. Together, this data suggests that the glutamatergic system may play a role in the pathophysiology and treatment of depression, and the agents, which more directly reduce glutamatergic neurotransmission, may represent a novel class of antidepressants.

Felbamate (Felbatol ® (Registered Trademark)) a dicarbamate, is FDA-approved as monotherapy and adjunctive therapy in adults with partial-onset seizures with or without secondary generalization and in partial and generalized seizures associated with Lennox-Gastaut syndrome in children. Felbamate has significant antiglutamatergic and neuroprotective properties, and may prove to have antidepressant properties in bipolar patients. In this study, we propose to investigate the potential efficacy of felbamate, which reduces glutamatergic throughput via inhibition of glutamate release and NMDA, AMPA, and metabotropic glutamate receptor blockade.

This is an 8-week randomized, double-blind, placebo-controlled study that will examine the efficacy and safety of felbamate in acutely depressed bipolar patients who are considered treatment-resistant.

This study has two phases. The first phase is the washout phase that will last for 7 days. The second phase is an 8-week acute treatment phase in which the efficacy and tolerability of felbamate and placebo are compared. Lithium can remain during Study Periods I and II if partial response to this agent is documented. Patients who complete the 8-week double-blind phase will receive clinical treatment. Acute efficacy will be determined by demonstrating a greater response rate using specified criteria.

Patients, ages 18 or older, with a diagnosis of Bipolar I and II disorder, depressed (without psychotic features), will be randomized to double-blind treatment to receive either felbamate (600-3000 mg/day) or placebo for a period of 8 weeks. Following this acute period, the patients will receive treatment as clinically indicated. Approximately 52 patients with treatment-resistant acute bipolar depression will be enrolled in the study.

Eligibility

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
Subjects may be included in the study only if they meet all of the following criteria:
Male or female subjects, 18 years or older.
Female subjects of childbearing potential must be using a medically accepted means of contraception.
Each subject must have a level of understanding sufficient to agree to all tests and examinations required by the protocol.
Each subject must understand the nature of the study and must sign an informed consent document.
Subjects must fulfill the criteria for Bipolar I or II disorder depressed without psychotic features as defined in DSM-IV based on clinical assessment and confirmed by structured diagnostic interview SCID-P.
Subjects must have an initial score at Visit 1 and Visit 2 of a least 20 on the MADRS.
Subjects must not have a decrease in the total score of MADRS of greater than or equal to 20% during washout (between Visits 1 and 2).
Meet criteria for treatment refractory depression operationally defined in appendix using the modified Antidepressant Treatment History Form (ATHF).
Subjects with a partial response to lithium may continue to take the medication during the trial; otherwise, subjects will proceed with a washout and monotherapy trial with felbamate.
Current major depressive episode of no less than 3 months.
EXCLUSION CRITERIA:
Subjects will be excluded from the study for any of the following reasons:
Currently taking a protocol disallowed agent that is effective and specifically necessary for that individual for the recurrence of mania.
Participation in a clinical trial of another investigational drug within 1 month (30 days) prior to study entry (Visit 1).
Female subjects who are either pregnant or nursing.
Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic or hematologic disease.
History of hepatic dysfunction.
Subjects with uncorrected hypothyroidism or hyperthyroidism.
Subjects with one or more seizures without a clear and resolved etiology.
Documented history of hypersensitivity to felbamate, meprobamate or other carbamates.
DSM-IV substance abuse (except nicotine and caffeine) within the past 30 days and substance dependence within the past 3 months or positive results for illicit drugs at prestudy drug screen.
Subjects with a rapid cycling course of illness (defined as 4 affective episodes in the previous year) in the past 12-months.
Treatment with an injectable depot neuroleptic within less than one dosing interval between depot neuroleptic injections prior to Visit 2.
Treatment with a reversible monoamine oxidase inhibitor, guanethidine, or guanadrel within 1 week prior to Visit 2.
Treatment with fluoxetine within 4 weeks prior to Visit 2.
Treatment with any other concomitant medication with primarily CNS activity, other than specified in Appendix A.
Treatment with clozapine or ECT within 12 weeks prior to Visit 2.
Current diagnosis of schizophrenia or other psychotic disorder as defined in the DSM-IV.
History of hypersensitivity or idiosyncratic reactions (e.g., rash, hepatitis, or cytopenia) to any drug.
History or current clinically significant immune disorders including autoimmune disease (e.g., systemic lupus erythematosus (SLE), autoimmune hemolytic anemia, autoimmune liver disease) or a history of any blood dyscrasia. Thus a history of anemias or cytopenias that were not obviously related to a limited benign process (e.g., anemia related to menstrual bleeding) will be reason for exclusion. Consultation with hematology will be used for help with any 'gray area' cases.
Judged clinically to be at serious suicidal risk, with a score of 3 or more on item 3 of the HAMD.

Location and Contact Information


Maryland
      National Institute of Mental Health (NIMH), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting
Patient Recruitment and Public Liaison Office  1-800-411-1222    prpl@mail.cc.nih.gov 
TTY  1-866-411-1010 

More Information

Detailed Web Page

Publications

Altamura CA, Mauri MC, Ferrara A, Moro AR, D'Andrea G, Zamberlan F. Plasma and platelet excitatory amino acids in psychiatric disorders. Am J Psychiatry. 1993 Nov;150(11):1731-3.

Auer DP, Putz B, Kraft E, Lipinski B, Schill J, Holsboer F. Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry. 2000 Feb 15;47(4):305-13.

Baumann B, Danos P, Krell D, Diekmann S, Wurthmann C, Bielau H, Bernstein HG, Bogerts B. Unipolar-bipolar dichotomy of mood disorders is supported by noradrenergic brainstem system morphology. J Affect Disord. 1999 Jul;54(1-2):217-24.

Study ID Numbers:  020176; 02-M-0176
Record last reviewed:  March 17, 2004
Last Updated:  March 17, 2004
Record first received:  April 24, 2002
ClinicalTrials.gov Identifier:  NCT00034229
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-27

Evaluation of the Genetics of Bipolar Disorder

This study is currently recruiting patients.

Sponsored by: National Institute of Mental Health (NIMH)
Information provided by: Warren G Magnuson Clinical Center (CC)

Purpose

The purpose of this study is to identify genes that may affect a person's chances of developing bipolar (BP) disorder and related conditions.

BP disorder is a serious and potentially life-threatening mood disorder. The condition can be inherited, but the mode of inheritance is poorly understood and probably involves multiple genes. This study will detect and localize genes that increase or decrease chances of developing BP disorder. Families with siblings who have bipolar disorder will be studied to obtain information for a national archival database of BP disorder genetic data.

Condition
Anxiety Disorder
Bipolar Disorder
Healthy
Mood Disorder
Schizophrenia

MedlinePlus related topics:  Anxiety;   Bipolar Disorder;   Mental Health;   Schizophrenia

Study Type: Observational
Study Design: Natural History

Official Title: Bipolar Genetics: A Collaborative Study

Further Study Details: 

Expected Total Enrollment:  2900

Study start: August 4, 1980

Bipolar affective disorder is a severe, heritable condition affecting about one percent of the population. The mode of inheritance is poorly understood and probably involves multiple loci of small to moderate effect. Genetic linkage has been reported to a number of chromosomal regions; some findings have been replicated. In 1988 the NIMH began a national archival database to search for susceptibility loci/genes in this condition. Its purpose was to collect a large sample of interviews and cell lines from families suitable for linkage and association studies. Since 1988, the NIMH-IRP has been an active site in this multi-center study. The protocol was originally supervised by Elliot Gershon, MD (1988-July 1998) and Dennis L. Murphy, MD (July 1998 - January 2004). In January 2004, Francis J. McMahon, M.D, took over supervision of the protocol. An expanded Consortium of sites concentrating on families identified through a sib pair was approved in August 1998 by the NIMH Extramural Program (MH 59535) via a competitive application. This Consortium added 450 new families and 2500 cell lines. Cell lines, clinical data, and 2 genome-wide sets of microsatellite genotypes have been made freely available to the scientific community under the auspices of the NIMH Center for Genetic Studies. In 2003, the IRB approved an amendment to expand the ascertainment criteria to include sib-pairs with a diagnosis of bipolar II disorder. Families ascertained in this manner are contributed to a second, large sample being collected in collaboration with The Johns Hopkins University and the University of Chicago, known as the CHIP study. In October 2003, the NIMH Extramural Program approved, via a competitive application, an additional 4 years of support for the Consortium collection, now including 11 extramural sites in addition to the IRP site. In this round, the focus will shift from affected sibling pairs to parent-affected offspring triads, with the goal of accruing a large sample suitable for future association studies. Both the Consortium and CHIP projects have similar study design and essentially identical recruitment, evaluation, and analysis procedures, so both projects are described together in what follows.

Eligibility

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION AND EXCLUSION CRITERIA:
The major goal of this project is to collect a sample of affected sibling pairs and cases with familial bipolar disorder, and to use this sample, along with control samples independently available, to identify vulnerability genes for bipolar disorder.
For the Consortium collection, the DSM-IV diagnosis of BPI is our definition of affected status. It is anticipated that a small number (less than 5%) of subjects ascertained as BPI is judged at the time of best estimate to have another diagnosis (primarily BPII, SA (BP) or organic mood disorder) and they are flagged in the dataset so as not to include them in primary analyses.
For the CHIP collection, we will screen families of treated BP I probands who by family history have at least 2 other siblings with recurrent major mood disorders including BP I, BP II, recurrent major depression, or schizoaffective disorder, bipolar type. This strategy has allowed us to include in our sample the full range of natural clinical variation associated with BPD.
Probands are recruited from a broad range of sources, including clinic populations, inpatient admissions, patient advocacy groups, and the public media. Prospective probands are asked to provide information about themselves and their first-degree relatives, using the screening and checklist questions for mood disorders contained in the FIGS. All probands aged 21 or over who can provide informed consent for interview and phlebotomy are enrolled.

Location and Contact Information


Maryland
      National Institute of Mental Health (NIMH), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting
Diane M. Kazuba  3014968977    kazubad@intra.nimh.nih.gov 

More Information

Detailed Web Page

Publications

Berrettini WH, Ferraro TN, Goldin LR, Weeks DE, Detera-Wadleigh S, Nurnberger JI Jr, Gershon ES. Chromosome 18 DNA markers and manic-depressive illness: evidence for a susceptibility gene. Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5918-21.

Detera-Wadleigh SD, Badner JA, Goldin LR, Berrettini WH, Sanders AR, Rollins DY, Turner G, Moses T, Haerian H, Muniec D, Nurnberger JI Jr, Gershon ES. Affected-sib-pair analyses reveal support of prior evidence for a susceptibility locus for bipolar disorder, on 21q. Am J Hum Genet. 1996 Jun;58(6):1279-85.

Dib C, Faure S, Fizames C, Samson D, Drouot N, Vignal A, Millasseau P, Marc S, Hazan J, Seboun E, Lathrop M, Gyapay G, Morissette J, Weissenbach J. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152-4.

Study ID Numbers:  800083; 80-M-0083
Record last reviewed:  July 27, 2004
Last Updated:  July 27, 2004
Record first received:  November 3, 1999
ClinicalTrials.gov Identifier:  NCT00001174
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-27

 

Next Page (More Trials)

 


 

ADVERTISEMENT
Advertisement
Disclaimer: The Bipolar Focus website provides information about bipolar disorder to interested viewers. This information is not a guide for patient treatment, nor is it meant to provide a substitute for professional advice about medical treatment of the disorder by a licensed physician or clinician. No medical advice is given, nor is any provided on or distributed from this website. Users interested in medical advice or treatment must consult a licensed practitioner. No doctor-patient relationship is created through the use of this web site.    

Copyright 1996-2006. Bipolar Focus - at www.moodswing.org - also, Schizophrenia.com. All Rights Reserved.