Bexarotene Augmentation of Antipsychotic Treatment for Chronic Schizophrenia

NCT00535574 | Completed Phase 3 DMC

• 1 other identifier: LRM250850
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 3

Brief Summary

Background: Bexarotene (Targretin) is a synthetic retinoid mainly used for treatment of patients suffer from oncological or dermatological diseases. The present study is based on: evidence that retinoids are involved in neurodevelopment ("the retinoid dysregulation hypothesis"); an assumption that the combined effect of antipsychotic agents and bexarotene will have a beneficial effect on schizophrenia patients; and the positive findings from our pilot open-label clinical trial (ClinicalTrials.gov Identifier: NCT00141947). However, clinical efficacy of bexarotene should be investigated in a placebo-controlled trial. Methods: In a 6-week, randomized, double-blind placebo-controlled trial Targretin (75 mg/day) or placebo capsules will be added to the stable ongoing antipsychotic treatment of 90 schizophrenia patients. Participants will be assessed at baseline and after 2, 4 and 6 weeks of treatment. A battery of research instruments will be used for assessment of psychopathology, side effects, general functioning and quality of life. In addition, cholesterol and triglyceride levels, liver and thyroid function tests and a blood cell count will be monitored at baseline and during the study

Conditions

Schizophrenia

Keywords

retinoids; bexarotene; schizophrenia; PANSS; Positive and negative symptoms of schizophrenia

Outcome Measures

Primary Outcomes (1)

• PANSS, CDSS, GAF, QLS

  every two weeks

Study Arms (2)

Bexarotene (Targretin LGD1069)

PLACEBO COMPARATOR

Drug: Bexarotene (Targretin LGD1069); Drug: bexarotene

placebo

ACTIVE COMPARATOR

Drug: Bexarotene (Targretin LGD1069)

Interventions

Bexarotene (Targretin LGD1069) DRUG

75 mg per day for 6 weeks

Bexarotene (Targretin LGD1069); placebo

bexarotene DRUG

75 mg/day 6 weeks

Bexarotene (Targretin LGD1069)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-60 years, male or female
• DSM-IV criteria for schizophrenia, or schizoaffective disorder.
• Ability and willingness to sign informed consent for participation in the study
• Stable blood parameters including adequate hematologic function, defined as WBC ≥ 4.300/μL, absolute neutrophil count ≥3.000/μL (\> 50%), and platelet count ≥ 180,000/μL; normal coagulation parameters; bilirubin ≤1.5 times the upper limit of normal (ULN); AST/ALT ≤ 2.5 × ULN; and serum creatinine ≤1.5 mg/dL.
• Only patients who had a normal baseline fasting triglyceride (FTG) level will be entered into the study; triglycerides may be normalized before study entry with use of an antilipemic agent.

You may not qualify if:

• Lipid abnormalities. Fasting triglyceride normal (normalization with an antilipemic allowed prior to study entry).
• Leucopenia or neutropenia. Hematopoietic: Hemoglobin at least 12.5 g/dL; WBC\< 4300/μL; Absolute neutrophil count \< 3000/μL; Platelet count \< 155,000/μL
• Evidence of organic brain damage, mental retardation, alcohol or drug abuse
• Impairment of renal function
• Hepatic dysfunction
• A history of pancreatitis
• Thyroid axis alterations
• Suicide attempt in past year.
• Cataracts.
• Systemic treatment with more than 15,000 IU of vitamin A daily.
• Patients with a known hypersensitivity to bexarotene or other components of the product.
• Pregnant women or a woman who intends to become pregnant.

Sponsors & Collaborators

• Beersheva Mental Health Center: lead

Study Sites (3)

Be'er Sheva Mental Health Center

Beersheba, Be'er Sheva, 84170, Israel

Location

Abarbanel Mental Health Center

Bat Yam, Israel

Location

Sha'ar Menashe Mental Health Center,

Hadera, Israel

Location

Related Publications (1)

• Lerner V, Miodownik C, Gibel A, Sirota P, Bush I, Elliot H, Benatov R, Ritsner MS. The retinoid X receptor agonist bexarotene relieves positive symptoms of schizophrenia: a 6-week, randomized, double-blind, placebo-controlled multicenter trial. J Clin Psychiatry. 2013 Dec;74(12):1224-32. doi: 10.4088/JCP.12m08160.

  PMID: 24434091 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

Bexarotene

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Prof. Vladimir Lerner, MD, PhD

  Be'er Sheva Mental Health Center Ben Gurion University of the Negev

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: A/Professor, Head of department

Study Record Dates

• First Submitted: September 24, 2007
• First Posted: September 26, 2007
• Study Start: November 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: May 1, 2011
• Last Updated: July 26, 2012

Record last verified: 2011-05

Locations

IL (3)