Pregnenolone Augmentation in the Treatment of Patients With Recent-Onset Schizophrenia (PREG-2008)

Pregnenolone Augmentation in the Treatment of Patients With Recent-Onset Schizophrenia: an 8-week, Randomized, Double-blind, Placebo-controlled Trial

Pregnenolone (PREG) is a neurosteroid, which displays multiple effects on the central nervous system, and may be beneficial in the treatment of patients with schizophrenia. Our recent 8-week, randomized, double-blind trial among patients with chronic schizophrenia and schizoaffective disorders, in which PREG versus placebo and DHEA have been added to conventional or atypical antipsychotics have yielded encouraging results with low-dose PREG (30 mg/day; ClinicalTrials.gov identifier NCT00140192; Ritsner et al., in press). The goal of the present study is to evaluate the potential role of PREG's augmentation compared to placebo in the treatment of young patients with newly diagnosed schizophrenia or schizophreniform or schizoaffective disorders.

In a 8-week, randomized, double-blind placebo-controlled trial PREG (50 mg/day) or placebo capsules will be added to the stable ongoing antipsychotic treatment of 60 patients with recent-onset schizophrenia or schizophreniform or schizoaffective disorders. Participants will be assessed at baseline and after 2, 4, 6 and 8 weeks of treatment. A battery of research instruments will be used for assessment of psychopathology, cognitive functions, side effects, general functioning and quality of life. In addition blood PREG levels will be monitored at baseline and during the study. The study is powered to detect moderate between-group effects on persistent positive, negative and cognitive symptoms.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizophreniform Disorder; Schizoaffective Disorders
• Intervention / Treatment: Dietary supplement: Pregnenolone; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Hadera, Israel, 38814
    • Shaar Menashe MHC and Tirat Carmel MHC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18-40 years of age, any ethnic group, either sex.
2. DSM-IV criteria for schizophrenia, schizophreniform or schizoaffective disorders (36).
3. Duration of illness less than 5 years since onset first psychotic episode.
4. Subjects entering the study must score at least 4 on the Clinical Global Impression Scale.
5. At least two weeks of ongoing treatment with current antipsychotic agents during the pre-treatment stabilization period.
6. Stable symptoms throughout the 2-week pre-treatment stabilization period. Clinical stability is defined as two consecutive weekly CGI ratings with no change in score, and with no more than a 20% change in PANSS total score.
7. No change in anticholinergic, benzodiazepine, or mood stabilizer medications for the pre-treatment stabilization period.
8. No anticipated need to alter any of the above medications (antipsychotics, anticholinergics, benzodiazepines, or mood stabilizers) for the 8-week duration of the study.
9. Ability to participate fully in the informed consent process, or have a legal guardian able to participate in the informed consent process.

Exclusion Criteria:

1. Evidence of serious neurologic or endocrine disorder, for example severe head trauma, seizure disorder, dementia, Cushings disease, or thyroid disorder, mental retardation, alcohol or drug abuse, substance dependence (other than nicotine dependence), or presenting symptoms likely substance-induced, as judged by a study physician.
2. Unstable medical illness or neurologic illness (seizures, CVA); history of prostate, breast, uterine, or ovarian cancer.
3. Pregnant women, use of oral contraceptives or other hormonal supplementation such as estrogen.
4. Current active suicidal and/or homicidal ideation, intent, or plan.
5. Known allergy to study medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1 Pregnenolone; 50 mg/day	Dietary supplement: Pregnenolone; 50 mg, caps.
PLACEBO_COMPARATOR: 2 Placebo; 1 caps.	Dietary supplement: Placebo; caps

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Clinical Global Impression Scale (CGI-S) The Positive and Negative Syndrome Scale (PANSS) The Scale for the Assessment of Negative Symptoms (SANS)	baseline, 2, 4, 6, and 8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Global Assessment of Functioning	baseline, 2, 4, 6, and 8 weeks
The Cambridge Neuropsychological Test Automated Battery (CANTAB)	baseline, 4 and 8 weeks
Extrapyramidal Symptom Rating Scale	baseline, 2, 4, 6, and 8 weeks

Collaborators and Investigators

• Sponsor: Sha'ar Menashe Mental Health Center
• Collaborators: Tirat Carmel Mental Health Center
• Investigators: Study Chair: Michael S Ritsher, MD, PhD, Technion and Shaar Menashe MHC; Study Director: Anatoly Kreinin, MD, PhD, Technion and Tirat Carmel Mental Health Center

Publications and helpful links

General Publications

• Ritsner M, Maayan R, Gibel A, Weizman A. Differences in blood pregnenolone and dehydroepiandrosterone levels between schizophrenia patients and healthy subjects. Eur Neuropsychopharmacol. 2007 Apr;17(5):358-65. doi: 10.1016/j.euroneuro.2006.10.001. Epub 2006 Nov 21.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (ACTUAL): December 1, 2010
• Study Completion (ACTUAL): December 1, 2010

Study Registration Dates

• First Submitted: February 18, 2009
• First Submitted That Met QC Criteria: February 18, 2009
• First Posted (ESTIMATE): February 19, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): December 15, 2010
• Last Update Submitted That Met QC Criteria: December 14, 2010
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Keywords: Schizophrenia; Augmentation; Pregnenolone; Neurosteroids
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Disease; Psychotic Disorders
• Other Study ID Numbers: MEN-8-11-08; 08TGF-1189 Stanley grant