Bipolar DisorderPhase 2NCT00025792
Clinical Trial of Pramipexole in Bipolar Depression
A Phase 2 study testing Pramipexole in people with Bipolar Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Pramipexole
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2001to Nov 2005
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Male or female subjects, 18 to 70 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.
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- 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 take VPA or lithium (valproate 50-125 microg/ml or lithium 0.6-1.2 mEq/L) for at least 4 weeks prior to Visit 2. At least two blood levels of lithium and VPA must be within therapeutic range (each at least 1 week apart) prior to Visit 2. If the subject is not taking lithium or VPA, the research physician may start them on lithium or VPA at the NIH.
- Current major depressive episode no more than 24 months.
Who cannot join
- 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.
Show all 17Show fewer
- 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 4 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Mental Health (NIMH)
Bethesda, Maryland, 20892
About this study
Official title: An Investigation of the Antidepressant Efficacy of a Dopamine Agonist With Neurotrophic Properties in Bipolar Disorder
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.
Read more
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.
Read the detailed description
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 70, 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.
- Conditions
- Bipolar Disorder
- Being tested
- Pramipexole
- Keywords
- Pramipexole, Neuroprotective, Placebo Controlled, Depression, Brain Imaging, Antidepressant, Bipolar Disorder, Bipolar, BPD, Bipolar Depression
- Medical subject headings
- Bipolar Disorder, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PramipexoleDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2001 (estimated)
- Study startOct 2001
- Study completionNov 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 200 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00025792
- Sponsor's protocol ID
- 020018
- Other IDs
- 02-M-0018
- Status last verified
- Nov 2005
- First submitted
- 24 Oct 2001
- Last updated
- 4 Mar 2008
- Results posted
- No
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. doi: 10.1097/00004714-199812000-00003.
PubMed 9864074Amsterdam JD, Garcia-Espana F. Venlafaxine monotherapy in women with bipolar II and unipolar major depression. J Affect Disord. 2000 Sep;59(3):225-9. doi: 10.1016/s0165-0327(99)00149-4.
PubMed 10854639Amsterdam JD, Berwish NJ. High dose tranylcypromine therapy for refractory depression. Pharmacopsychiatry. 1989 Jan;22(1):21-5. doi: 10.1055/s-2007-1014572.
PubMed 2710808Mah L, Zarate CA Jr, Nugent AC, Singh JB, Manji HK, Drevets WC. Neural mechanisms of antidepressant efficacy of the dopamine receptor agonist pramipexole in treatment of bipolar depression. Int J Neuropsychopharmacol. 2011 May;14(4):545-51. doi: 10.1017/S1461145710001203. Epub 2010 Oct 29.
PubMed 21029512
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigation of the Antidepressant Efficacy of a Dopamine Agonist With Neurotrophic Properties in Bipolar Disorder
- ClinicalTrials.gov ID
- NCT00025792
- Acronym / sponsor ID
- 020018
- Conditions
- Bipolar Disorder
- Keywords
- Pramipexole, Neuroprotective, Placebo Controlled, Depression, Brain Imaging, Antidepressant, Bipolar Disorder, Bipolar
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- Oct 2001
- Study completion
- Nov 2005
- First posted
- 25 Oct 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 70, 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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female subjects, 18 to 70 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pramipexole | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 9864074Amsterdam 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. doi: 10.1097/00004714-199812000-00003.
- Background: PubMed 10854639Amsterdam JD, Garcia-Espana F. Venlafaxine monotherapy in women with bipolar II and unipolar major depression. J Affect Disord. 2000 Sep;59(3):225-9. doi: 10.1016/s0165-0327(99)00149-4.
- Background: PubMed 2710808Amsterdam JD, Berwish NJ. High dose tranylcypromine therapy for refractory depression. Pharmacopsychiatry. 1989 Jan;22(1):21-5. doi: 10.1055/s-2007-1014572.
- Derived from this study: PubMed 21029512Mah L, Zarate CA Jr, Nugent AC, Singh JB, Manji HK, Drevets WC. Neural mechanisms of antidepressant efficacy of the dopamine receptor agonist pramipexole in treatment of bipolar depression. Int J Neuropsychopharmacol. 2011 May;14(4):545-51. doi: 10.1017/S1461145710001203. Epub 2010 Oct 29.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pramipexole in people with Bipolar Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00025792, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.