SchizophreniaNCT01831986
Pregnenolone and L-theanine Augmentation in the Treatment for Schizophrenia and Schizoaffective Disorders
A study testing Pregnenolone and L-Theanine in people with Schizophrenia and Schizoaffective Disorder, run by Sha'ar Menashe Mental Health Center.
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. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder
- What is being tested?
- Pregnenolone and L-Theanine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- Jan 2011to Dec 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
About this study
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
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
Read the 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.
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Being tested
- Pregnenolone and L-Theanine, Placebo
- Keywords
- Schizophrenia, Schizoaffective disorder, Pregnenolone, L-Theanine, Augmentation
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pregnenolone and L-TheanineDietary supplement
Pregnenolone (50 mg/day) with L-theanine (400 mg/day)
PlaceboOther
Caps
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Dietary Supplement: Pregnenolone and L-Theanine |
| Sugar caps. | Placebo comparator | Placebo (4 caps/day) Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Positive and Negative Syndrome Scale
Measured: 2 weeks
Secondary outcomes (8)
Extrapyramidal Symptom Rating Scale
Measured: 2 weeks
Barnes Akathisia Scale
Measured: 2 weeks
The Liverpool University Neuroleptic Side Effect Rating Scale
Measured: 4 weeks
Global Assessment of Functioning
Measured: 4 weeks
Subjective Scale to Investigate Cognition in Schizophrenia
Measured: 4 weeks
Quality of Life Enjoyment and Satisfaction Questionnaire - Abbreviated version (Q-LES-Q-18)
Measured: 4 weeks
SANS
Measured: 2 weeks
Hamilton Anxiety Scale
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2013 (estimated)
- Study startJan 2011
- Primary completionDec 2013 (estimated)
- Study completionDec 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sha'ar Menashe Mental Health Center
- Sponsor type
- University, hospital or other
- Collaborators
- Tirat Carmel Mental Health Center
- Responsible party
- Principal investigator, Michael Ritsner, MD, PhD, Sha'ar Menashe Mental Health Center
- Investigators
- Michael S Ritsner, MD, PhD, Principal investigator, Shaar Menashe MHC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01831986
- Sponsor's protocol ID
- 13-9-10
- Status last verified
- Dec 2013
- First submitted
- 14 Dec 2010
- Last updated
- 5 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 20584515Ritsner 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.
PubMed 20070787Ritsner 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.
PubMed 17123790Kardashev 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.
PubMed 26218236
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01831986
- Acronym / sponsor ID
- 13-9-10
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Keywords
- Schizophrenia, Schizoaffective disorder, Pregnenolone, L-Theanine, Augmentation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Sha'ar Menashe Mental Health CenterUniversity, hospital or other
- Collaborators
- Tirat Carmel Mental Health Center
- Study start
- Jan 2011
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Dec 2013 (estimated)
- First posted
- 15 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pregnenolone + L-Theanine | Experimental | Dietary Supplement: Pregnenolone and L-TheanineThe 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. |
| Sugar caps. | Placebo comparator | Other: PlaceboPlacebo (4 caps/day) |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.].
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pregnenolone and L-TheaninePregnenolone (50 mg/day) with L-theanine (400 mg/day) | Dietary supplement | Pregnenolone + L-Theanine |
| PlaceboCaps | Other | Sugar caps. |
Primary outcome
The Positive and Negative Syndrome Scale
Time frame: 2 weeks
8 secondary outcomes
Extrapyramidal Symptom Rating Scale
Time frame: 2 weeks
Barnes Akathisia Scale
Time frame: 2 weeks
The Liverpool University Neuroleptic Side Effect Rating Scale
Time frame: 4 weeks
Global Assessment of Functioning
Time frame: 4 weeks
Subjective Scale to Investigate Cognition in Schizophrenia
Time frame: 4 weeks
Quality of Life Enjoyment and Satisfaction Questionnaire - Abbreviated version (Q-LES-Q-18)
Time frame: 4 weeks
SANS
Time frame: 2 weeks
Hamilton Anxiety Scale
Time frame: 2 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2013.
- Background: PubMed 20584515Ritsner 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.
- Background: PubMed 20070787Ritsner 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.
- Background: PubMed 17123790Ritsner 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.
- Derived from this study: PubMed 26218236Kardashev 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael S Ritsner, MD, PhD principal investigator
Shaar Menashe MHC
Questions about this trial
What is this clinical trial studying?
A study testing Pregnenolone and L-Theanine in people with Schizophrenia and Schizoaffective Disorder, run by Sha'ar Menashe Mental Health Center.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Positive and Negative Syndrome Scale (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01831986, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2013.