Pregnenolone and L-theanine Augmentation in the Treatment for Schizophrenia and Schizoaffective Disorders

Sponsor

Sha'ar Menashe Mental Health Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT01831986

Collaborator

Tirat Carmel Mental Health Center (Other)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

Schizophrenia (SZ) and schizoaffective (SA) disorders are comprised of several debilitating symptoms. It was suggested that compounds with neuroprotective effects might be useful in the management of SZ/SA symptoms. Our previous clinical trials indicated significant beneficial effects for augmentations with two different neuroprotective agents: Pregnenolone and L-Theanine. Pregnenolone (PREG) is a neurosteroid, which displays multiple effects on the central nervous system. Our recent 8-week, randomized, double-blind trial among patients with chronic SZ/SA disorders, in which PREG versus placebo and DHEA was added to antipsychotics, yielded encouraging results: PREG augmentation demonstrated significant amelioration of positive symptoms, EPS, as well as an improvement in attention, and working memory performance of SZ/SA disorder patients (Ritsner et al 2010). L-Theanine is a unique amino acid present almost exclusively in the tea plant. It possesses neuroprotective, mood-enhancing, and relaxation activities. L-theanine augmentation to antipsychotic therapy can ameliorate positive, activation, and anxiety symptoms in SZ/SA disorder patients (grant # 06TGF-911, (Ritsner et al 2010). This proposed study would extend our prior research with Pregnenolone and L-theanine by combining both agents versus placebo. We hypothesized that addition of both these compounds to ongoing antipsychotics would significantly improve the clinical status of SZ/SA patients.

Methods: In an 8-week, randomized, double-blind placebo-controlled trial a combination of PREG (50 mg/day) with L-theanine (400 mg/day) versus placebo will be added to the stable ongoing antipsychotic treatment of 200 patients with schizophrenia or schizoaffective disorders. This trial will be conducted at five sites in Israel. 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 the assessment of psychopathology, side effects, general functioning and quality of life

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Schizoaffective Disorder	Dietary Supplement: Pregnenolone and L-Theanine Other: Placebo	N/A

Detailed Description

This is a two-year randomized placebo-controlled double-blind investigation of the augmentation of PREG with L-theanine in the management of patients with SZ/SA. The study will consist of two phases: a 2-week continued stability (lead in) phase and an 8-week double-blind treatment phase. In the lead-in phase, patients receiving antipsychotic medication will remain on their maintenance regimen for at least two weeks. 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. The treatment phase will be 8-week parallel groups, placebo-controlled, double-blind trial of adjunctively administered PREG with L-theanine or placebo. Assignment to PREG with L-theanine or placebo will be on a random, stratified (i.e., FGAs/SGAs, inpatient/outpatient) basis. PREG (50 mg/day) with L-theanine (400 mg/day) and placebo will be administered in divided doses in the form of capsules. If a patient relapses during the treatment phase of the study, the patient will be removed from the study. All attempts will be made to obtain end-of-study ratings. If such measures cannot be obtained, four- and six-week data, if collected prior to relapse, will be informative. Patients who fulfill the entry criteria will enter the 8-week double-blind treatment phase of the study. Assignment to PREG with L-theanine or placebo will be on a random, stratified (i.e., conventional/new generation antipsychotic treatment, inpatient/outpatient) basis. PREG (50 mg/day) with L-theanine (400 mg/day)/placebo will be administered in divided doses in the form of white capsules. If a patient relapses during the treatment phase of the study, the patient will be removed from the study. All attempts will be made to obtain end-of-study ratings. If such measures cannot be obtained, four- and eight-week data, if collected prior to relapse, will be informative.

Subjects will be assessed at baseline and after 2, 4, 6, and 8 weeks of treatment using psychiatric rating scales, and self-report questionnaires. Neurobiological (plasma cortisol, PREG, dehydroepiandrosterone, BDNF and other biologically active molecules) and immunological (the pro-inflammatory cytokines and others) testing will be conducted at baseline, and after treatment. The efficacy and safety of augmenting antipsychotic treatment of PREG with L-theanine will be analyzed.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Addition of Both Pregnenolone and L-theanine to Ongoing Antipsychotic Treatment for Schizophrenia and Schizoaffective Disorders: an 8-week, Randomized, Double-blind, Placebo-controlled Multicenter Study

Study Start Date :

Jan 1, 2011

Anticipated Primary Completion Date :

Dec 1, 2013

Anticipated Study Completion Date :

Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pregnenolone + L-Theanine The 60 participating subjects will be randomized into 2 groups: 30 patients will receive PREG (50 mg/day) with L-theanine (400 mg/day) and 30 patients will receive a placebo, each for 8 weeks in a double-blind manner.	Dietary Supplement: Pregnenolone and L-Theanine Pregnenolone (50 mg/day) with L-theanine (400 mg/day)
Placebo Comparator: Sugar caps. Placebo (4 caps/day)	Other: Placebo Caps

Arm

Intervention/Treatment

Experimental: Pregnenolone + L-Theanine

The 60 participating subjects will be randomized into 2 groups: 30 patients will receive PREG (50 mg/day) with L-theanine (400 mg/day) and 30 patients will receive a placebo, each for 8 weeks in a double-blind manner.

Dietary Supplement: Pregnenolone and L-Theanine

Pregnenolone (50 mg/day) with L-theanine (400 mg/day)

Placebo Comparator: Sugar caps.

Placebo (4 caps/day)

Other: Placebo

Caps

Outcome Measures

Primary Outcome Measures

The Positive and Negative Syndrome Scale [2 weeks]

Secondary Outcome Measures

Extrapyramidal Symptom Rating Scale [2 weeks]
Barnes Akathisia Scale [2 weeks]
The Liverpool University Neuroleptic Side Effect Rating Scale [4 weeks]
Global Assessment of Functioning [4 weeks]
Subjective Scale to Investigate Cognition in Schizophrenia [4 weeks]
Quality of Life Enjoyment and Satisfaction Questionnaire - Abbreviated version (Q-LES-Q-18) [4 weeks]
SANS [2 weeks]
Hamilton Anxiety Scale [2 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18-50 years, men or women.
DSM-IV criteria for schizophrenia or schizoaffective disorder (American Psychiatric Association 2000).
Subjects entering the study must score at least 4 on the Clinical Global Impression Scale (CGI-S).
At least two weeks of ongoing treatment with current antipsychotic agents.
No change in anticholinergic, or benzodiazepine medications for the pre-treatment stabilization period.
Stable symptoms throughout the 2 week pre-treatment stabilization period.
Ability and willingness to sign an informed consent form for participation in the study.

Exclusion Criteria:

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.
Unstable medical illness or neurologic illness (seizures, CVA); breast, uterine, or ovarian cancer.
Patients with impaired renal function or with a history of significant impaired renal function will be excluded.
Patients with significant suicidal risk will be excluded.
Pregnant women, use of oral contraceptives or other hormonal supplementation such as estrogen. [Female patients will also have a pregnancy test.].
Known allergy to study medication.
Patients receiving mood-stabilizing medications.