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

NCT01831986 | Unknown DMC

• 1 other identifier: 13-9-10
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

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

Conditions

Schizophrenia; Schizoaffective Disorder

Keywords

Schizophrenia; Schizoaffective disorder; Pregnenolone; L-Theanine; Augmentation

Outcome Measures

Primary Outcomes (1)

• The Positive and Negative Syndrome Scale

  2 weeks

Secondary Outcomes (8)

• 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

Study Arms (2)

Pregnenolone + L-Theanine

EXPERIMENTAL

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

Sugar caps.

PLACEBO COMPARATOR

Placebo (4 caps/day)

Other: Placebo

Interventions

Pregnenolone and L-Theanine DIETARY_SUPPLEMENT

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

Pregnenolone + L-Theanine

Placebo OTHER

Caps

Sugar caps.

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sha'ar Menashe Mental Health Center: lead
• Tirat Carmel Mental Health Center: collaborator

Related Publications (4)

• 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.

  PMID: 20584515 BACKGROUND

• 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.

  PMID: 20070787 BACKGROUND

• 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.

  PMID: 17123790 BACKGROUND

• Kardashev A, Ratner Y, Ritsner MS. Add-On Pregnenolone with L-Theanine to Antipsychotic Therapy Relieves Negative and Anxiety Symptoms of Schizophrenia: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Trial. Clin Schizophr Relat Psychoses. 2018 Spring;12(1):31-41. Epub 2015 Jul 28.

  PMID: 26218236 DERIVED

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Pregnenolone; theanine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Study Officials

• Michael S Ritsner, MD, PhD

  Shaar Menashe MHC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head, Acute Department

Study Record Dates

• First Submitted: December 14, 2010
• First Posted: April 15, 2013
• Study Start: January 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 5, 2013

Record last verified: 2013-12