Simvastatin Augmentation of Lithium Treatment in Bipolar Depression

This study is currently recruiting participants.
Verified November 2013 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Roy Perlis, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01665950
First received: April 9, 2012
Last updated: November 7, 2013
Last verified: November 2013
  Purpose

Primary Aim: To estimate the antidepressant efficacy of simvastatin versus placebo as an adjunct to lithium, valproate, and/or other atypical antipsychotic therapy among individuals with bipolar I disorder in a nonpsychotic major depressive episode.

Hypothesis: Simvastatin will be superior to placebo in improvement of depressive symptoms assessed by the Montgomery-Asberg Depression Rating Scale (MADRS).


Condition Intervention Phase
Bipolar Disorder
Drug: Simvastatin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Simvastatin Augmentation of Lithium Treatment in Bipolar Depression

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Change in MADRS (4 weeks) [ Time Frame: Baseline vs week 4 (and, for placebo nonresponders in 1st 4 weeks, week 8 vs week 4) ] [ Designated as safety issue: No ]
    Change in Montgomery-Asberg Depression Rating Scale (MADRS) in simvastatin-treated epochs versus placebo-treated epochs


Estimated Enrollment: 30
Study Start Date: August 2012
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Simvastatin-Simvastatin
Subjects will receive simvastatin in phase 1 (4 weeks) and phase 2 (4 weeks)
Drug: Simvastatin
The study uses the Sequential Parallel Comparison design (SPCD), with two 4-week phases: n=30 subjects are randomized 1:1 to simvastatin versus placebo add-on for 4 weeks, with the nonresponders re-randomized 1:1 for a further 4 weeks. The SPCD will allow us to pool data from both phases to estimate the simvastatin treatment effect. Subjects who respond in phase 1, and all subjects who receive simvastatin in phase 1, continue blinded treatment in phase 2 to preserve the blind, but only phase 1 results are analyzed. Dosage for simvastatin or matched placebo 20mg daily for 8 weeks.
Experimental: Placebo->Simvastatin
Placebo non-responders after the 1st 4 weeks will be re-randomized 1:1 to placebo or simvastatin for the next 4 weeks
Drug: Simvastatin
The study uses the Sequential Parallel Comparison design (SPCD), with two 4-week phases: n=30 subjects are randomized 1:1 to simvastatin versus placebo add-on for 4 weeks, with the nonresponders re-randomized 1:1 for a further 4 weeks. The SPCD will allow us to pool data from both phases to estimate the simvastatin treatment effect. Subjects who respond in phase 1, and all subjects who receive simvastatin in phase 1, continue blinded treatment in phase 2 to preserve the blind, but only phase 1 results are analyzed. Dosage for simvastatin or matched placebo 20mg daily for 8 weeks.
Drug: Placebo
Subjects (n=15) are randomized to placebo add-on for 4 weeks, with the nonresponders re-randomized 1:1 to statin vs placebo for a further 4 weeks. Subjects who respond in phase 1 continue blinded treatment in phase 2 to preserve the blind, but only phase 1 results are analyzed. Dosage for simvastatin or matched placebo 20mg daily for 8 weeks.
Placebo Comparator: Placebo-Placebo
Placebo nonresponders for the 1st 4 weeks will be re-randomized 1:1 to placebo or simvastatin for the subsequent 4 weeks
Drug: Placebo
Subjects (n=15) are randomized to placebo add-on for 4 weeks, with the nonresponders re-randomized 1:1 to statin vs placebo for a further 4 weeks. Subjects who respond in phase 1 continue blinded treatment in phase 2 to preserve the blind, but only phase 1 results are analyzed. Dosage for simvastatin or matched placebo 20mg daily for 8 weeks.

Detailed Description:

(see brief summary)

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion:

  • Age 18-65
  • written informed consent
  • meets DSM-IV criteria (by SCID-I/P) for bipolar I disorder, current episode depressed
  • MADRS score of at least 20 (i.e., moderate depression) and no greater than 34 (i.e., severe depression) at screen and baseline visit
  • YMRS score < 12 at screen and baseline visit
  • currently treated with a lithium preparation (carbonate or citrate) at stable dose for at least 4 wks with level >0.4 and <1.0; and/or valproate at stable dose for at least 4 wks at level >60 and <110; and/or other atypical antipsychotic at stable dose for at least 4 weeks (at least minimum FDA-labeled dose).

Exclusion:

  • Psychotic features in the current episode, as assessed by YMRS item #8>6
  • felt by the study clinician to require inpatient hospitalization for adequate management
  • more than 3 failed pharmacologic interventions in the current major depressive episode, exclusive of primary mood stabilizer
  • current substance use disorder other than nicotine, by SCID-I/P
  • pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (to include oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine device, tubal ligation, or partner with vasectomy)
  • women who are breastfeeding
  • serious suicide or homicide risk, as assessed by evaluating clinician
  • other unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease, based on review of medical history, physical examination, and screening laboratory tests
  • patients who have taken an investigational psychotropic drug within the last 30 days
  • patients receiving additional anticonvulsant, antipsychotic, or antidepressant within 1 week prior to study entry
  • patients requiring continued treatment with excluded medications (see below).

Excluded medications: other statins, which could influence Wnt signaling; any other drug known to interact with simvastatin, including potent inhibitors/inducers of CYP3A4 such as itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, voriconazole, cyclosporine or danazol; gemfibrozil or other lipid-lowering drugs that can cause myopathy when given alone; amiodarone, ranolazine, verapamil, diltiazem, or amlodipine; niacin; digoxin; coumarin anticoagulants; colchicine; nefazodone; protease inhibitors including ritonavir, indinavir, nelfinavir, or saquinavir.

Allowed: benzodiazepines and sedative-hypnotic agents if dosage has been stable for 2 weeks prior to study entry; thyroid or estrogen replacement provided dosage has been stable for 1 month; antidepressants, antipsychotics, and anticonvulsants provided dosage has been stable for 1 week prior to study entry.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01665950

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Roy H Perlis, MD, MSc    617-726-7426    rperlis@chgr.mgh.harvard.edu   
Principal Investigator: Roy H Perlis, MD MSc         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Roy H Perlis, MD, MSc Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Roy Perlis, Associate Professor of Psychiatry, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01665950     History of Changes
Other Study ID Numbers: 2011P002545
Study First Received: April 9, 2012
Last Updated: November 7, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Bipolar Disorder
Depression
Depressive Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Behavioral Symptoms
Simvastatin
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014