Bexarotene Augmentation of Antipsychotic Treatment for Chronic Schizophrenia

Bexarotene Augmentation of Antipsychotic Treatment for Chronic Schizophrenia: a 6-week, Randomized, Double-blind Placebo-controlled Trial

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

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Bexarotene (Targretin LGD1069); Drug: bexarotene

Detailed Description

Recruiting was beginning on November 2008

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 3

Contacts and Locations

Study Locations

• Israel
  • Bat-Yam, Israel
    • Abarbanel Mental Health Center
  • Hadera,, Israel
    • Sha'ar Menashe Mental Health Center,
  • Be'er Sheva
    • Be'er Sheva,, Be'er Sheva, Israel, 84170
      • Be'er Sheva Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-60 years, male or female
2. DSM-IV criteria for schizophrenia, or schizoaffective disorder.
3. Ability and willingness to sign informed consent for participation in the study
4. 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.
5. 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.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Bexarotene (Targretin LGD1069)	Drug: Bexarotene (Targretin LGD1069); 75 mg per day for 6 weeks; Drug: bexarotene; 75 mg/day 6 weeks
Active Comparator: placebo	Drug: Bexarotene (Targretin LGD1069); 75 mg per day for 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PANSS, CDSS, GAF, QLS	every two weeks

Collaborators and Investigators

• Sponsor: Beersheva Mental Health Center
• Investigators: Principal Investigator: Prof. Vladimir Lerner, MD, PhD, Be'er Sheva Mental Health Center Ben Gurion University of the Negev

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: September 24, 2007
• First Submitted That Met QC Criteria: September 24, 2007
• First Posted (Estimate): September 26, 2007

Study Record Updates

• Last Update Posted (Estimate): July 26, 2012
• Last Update Submitted That Met QC Criteria: July 25, 2012
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: schizophrenia; bexarotene; PANSS; retinoids; Positive and negative symptoms of schizophrenia
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Antineoplastic Agents; Bexarotene
• Other Study ID Numbers: LRM250850