Clinical Trial of Pramipexole in Bipolar Depression

NCT00025792 | Completed Phase 2

• 2 other identifiers: 02001802-M-0018
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Bipolar Disorder

Keywords

Pramipexole; Neuroprotective; Placebo Controlled; Depression; Brain Imaging; Antidepressant; Bipolar Disorder; Bipolar; BPD; Bipolar Depression

Interventions

Pramipexole DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institute of Mental Health (NIMH)

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 9864074 BACKGROUND

• 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. doi: 10.1016/s0165-0327(99)00149-4.

  PMID: 10854639 BACKGROUND

• Amsterdam JD, Berwish NJ. High dose tranylcypromine therapy for refractory depression. Pharmacopsychiatry. 1989 Jan;22(1):21-5. doi: 10.1055/s-2007-1014572.

  PMID: 2710808 BACKGROUND

• Mah 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.

  PMID: 21029512 DERIVED

MeSH Terms

Conditions

Bipolar Disorder; Depression

Interventions

Pramipexole

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Benzothiazoles; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: October 24, 2001
• First Posted: October 25, 2001
• Study Start: October 1, 2001
• Study Completion: November 1, 2005
• Last Updated: March 4, 2008

Record last verified: 2005-11

Locations

US (1)