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

Schizophrenia Clinical Trial

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT01831986
• Other study ID #: 13-9-10
• Status: Enrolling by invitation
• Phase: N/A
• First received: December 14, 2010
• Last updated: December 4, 2013
• Start date: January 2011
• Est. completion date: December 2013

Study information

• Verified date: December 2013
• Source: Sha’ar Menashe Mental Health Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 60
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia

Intervention

Dietary Supplement:
• Pregnenolone and L-Theanine
Pregnenolone (50 mg/day) with L-theanine (400 mg/day)

Other:
• Placebo
Caps

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Sha’ar Menashe Mental Health Center	Tirat Carmel Mental Health Center

References & Publications (3)

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. Epub 2006 Nov 21. — View Citation

Ritsner MS, Gibel A, Shleifer T, Boguslavsky I, Zayed A, Maayan R, Weizman A, Lerner V. Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial. J Clin Psychiatry. 2010 Oct;71(10):1351-62. doi: 10.4088/JCP.09m05031yel. Epub 2010 Jun 15. — View Citation

Ritsner MS. Pregnenolone, dehydroepiandrosterone, and schizophrenia: alterations and clinical trials. CNS Neurosci Ther. 2010 Spring;16(1):32-44. doi: 10.1111/j.1755-5949.2009.00118.x. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Positive and Negative Syndrome Scale		2 weeks	No
Secondary	Extrapyramidal Symptom Rating Scale		2 weeks	Yes
Secondary	Barnes Akathisia Scale		2 weeks	Yes
Secondary	The Liverpool University Neuroleptic Side Effect Rating Scale		4 weeks	Yes
Secondary	Global Assessment of Functioning		4 weeks	No
Secondary	Subjective Scale to Investigate Cognition in Schizophrenia		4 weeks	No
Secondary	Quality of Life Enjoyment and Satisfaction Questionnaire - Abbreviated version (Q-LES-Q-18)		4 weeks	No
Secondary	SANS		2 weeks	Yes
Secondary	Hamilton Anxiety Scale		2 weeks	Yes