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Simvastatin Augmentation of Lithium Treatment in Bipolar Depression

This study has been terminated.
(Lack of enrollment)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01665950
First Posted: August 16, 2012
Last Update Posted: May 9, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Roy Perlis, Massachusetts General Hospital
  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
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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 Roy Perlis, 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) ]
    Change in Montgomery-Asberg Depression Rating Scale (MADRS) in simvastatin-treated epochs versus placebo-treated epochs


Enrollment: 4
Study Start Date: August 2012
Study Completion Date: October 2014
Primary Completion Date: October 2014 (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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion:

  • Age 18-65
  • written informed consent
  • meets Diagnostic and Statistical Manual - IV (DSM-IV) criteria (by Structured Clinical Interview for DSM-IV (SCID-I/P)) for bipolar I disorder, current episode depressed
  • Montgomery-Asberg Depression Scale (MADRS) score of at least 20 (i.e., moderate depression) and no greater than 34 (i.e., severe depression) at screen and baseline visit
  • Young Mania Rating Scale (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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01665950


Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Roy H Perlis, MD, MSc Massachusetts General Hospital
  More Information

Responsible Party: Roy Perlis, Associate Professor of Psychiatry, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01665950     History of Changes
Other Study ID Numbers: 2011P002545
First Submitted: April 9, 2012
First Posted: August 16, 2012
Results First Submitted: November 30, 2016
Results First Posted: February 23, 2017
Last Update Posted: May 9, 2017
Last Verified: April 2017

Additional relevant MeSH terms:
Depression
Bipolar Disorder
Behavioral Symptoms
Bipolar and Related Disorders
Mental Disorders
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors