Withania Somnifera: an Immunomodulator and Anti-inflammatory Agent for Schizophrenia
Keywords
Abstract
Description
The primary aim is to determine whether a standardized extract of Withania somnifera will reduce psychopathology scores (PANSS total) and stress scores(PSS total) in persons with schizophrenia?
The study will also determine whether WSE reduces measures of positive and negative and general symptoms of schizophrenia (PANSS subscale scores)?
Another primary aim will be to determine if changes in antipsychotic and/or other psychotropic medications (lithium, anticonvulsants, antidepressants, anxiolytic agents or hypnotics) (examples: dosage escalation or reductions or switch or stoppage) will favor the group receiving the standardized Withania somnifera extract versus those receiving placebo. Even though we expect changes in antipsychotic medications to occur when patients experience an exacerbation of psychotic symptoms (or other psychiatric symptoms), we hypothesize that those receiving the standardized Withania somnifera extract will experience fewer medication adjustments then those assigned to placebo.
A secondary aim is to determine whether WSE will rebalance TH1/TH2 ratios (cytokine measures) and mediate a reduction of elevated hs-CRP levels? The study will assess whether those subjects whose TH1/TH2 ratios normalize have a greater magnitude of clinical improvement vs. those subjects whose immune ratios remain unbalanced. Similarly, the study will assess whether reduction of hsCRP levels correlate with improvements in PANSS total and subscale scores or the PSS total scores.
Eighty or more patients with DSM IV TR (or if instituted by the study initiation: DSM V) schizophrenia or schizoaffective disorder will be screened and 60 or more eligible patients will be enrolled in a 12 week placebo controlled double blind study. Subjects who have experienced an exacerbation of positive symptoms (delusions, hallucinations, etc). Subjects receiving medications that affect the immune-inflammatory system will be excluded and those receiving antibiotics, antiviral or anti-parasitic medications will be excluded.
Base line laboratory and EKG examination will be carried out to establish eligibility for study participation. In addition specific laboratory analyses of immune markers namely interleukin-2, interferon gamma, interleukin-4, interleukin 6 and high sensitivity C-Reactive Protein will be carried out.
Sixty or more patients will be randomly assigned to receive either WSE or matching placebo starting with 1 capsule of 250 mg strength twice a day (total daily dose = 500 mg) for the first week which will be increased to 2 capsules of 250 mg twice daily (total daily dose = 1000 mg) for a total treatment period of 12 weeks. An assessment of psychopathology (PANSS) and stress will be carried out at each scheduled visit. Assessments of safety including vital signs and treatment emergent adverse events will also be carried out at each visit. Immune-inflammatory markers will be re-assessed at the final visit.
Dates
| Last Verified: | 09/30/2017 |
| First Submitted: | 02/11/2013 |
| Estimated Enrollment Submitted: | 02/14/2013 |
| First Posted: | 02/17/2013 |
| Last Update Submitted: | 12/07/2017 |
| Last Update Posted: | 01/02/2018 |
| Date of first submitted results: | 07/06/2017 |
| Date of first submitted QC results: | 10/19/2017 |
| Date of first posted results: | 11/21/2017 |
| Actual Study Start Date: | 03/31/2013 |
| Estimated Primary Completion Date: | 07/06/2016 |
| Estimated Study Completion Date: | 07/06/2016 |
Condition or disease
Intervention/treatment
Drug: Sensoril®
Drug: Placebo
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: Sensoril® Sensoril® is a proprietary extract of Withania Somnifera | Drug: Sensoril® Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera |
| Placebo Comparator: Placebo Placebo | Drug: Placebo Each Placebo capsule comprises inert ingredients; microcrystalline cellulose NF 102, croscarmellose Sodium NF, silicon Dioxide, Fumed NF (Cab-0-sil), magnesium sterate, NF matched in appearance and fill weight to Sensoril® capsules. Moreover, based on past experience, we will expose the placebo capsules to covered sachets containing Sensoril, so that the smell permeates the placebo capsules which then smell like the Sensoril capsules. |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: 1. Adult males or females (≥ 18 years, to 75 years) 2. DSM IV TR diagnosis of schizophrenia or schizoaffective disorder (If officially instituted by study initiation: DSM V diagnoses will be used). 3. Ability to provide informed written consent 4. PANSS total score ≥ 60, positive symptom cluster, (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, hostility and unusual thought content with at least 2 items scoring ≥ 4, or one of these items scoring ≥ 5, on a scale ranging from 1 = absent to 7 = extreme 5. Current symptom exacerbation ≥ 2 weeks, but ≤ 1 year 6. Receiving anti-psychotic medications for ≥ 4 weeks 7. For women of child bearing age, a negative pregnancy test at screening. Exclusion Criteria: 1. Testing positive for illicit substances (marijuana or alcohol use will be assessed on a case by case basis, caffeine and nicotine are excepted) 2. Receiving pharmacological treatment for addictions (naltrexone, suboxone, acamprosate, others) will be reviewed on a case by case basis 3. Seriously unstable medical illnesses 4. Pregnant or breast feeding women 5. Known allergy or history of serious adverse event with WSE 6. Subjects who may require imminent hospitalization (examples: suicidal or aggressive behavior) 7. Currently receiving antibiotics, anti-viral, or anti-parasitic medications 8. Currently receiving immunosuppressive medications (e.g. corticosteroids, chemotherapy or transplantation or HIV/AIDs associated drugs). 9. Currently receiving NSAIDs or Aspirin (>81 mg/day) on a daily basis or PRN use > 2x/week (in the last 4 weeks). |
Outcome
Primary Outcome Measures
1. Positive and Negative Syndrome Scale (PANSS) [Baseline and 12 Weeks]
Secondary Outcome Measures
1. Perceived Stress Scale (PSS) [Baseline and 12 weeks or end of treatment]
2. Clinical Global Impression Scale (CGI-S) - Severity [Baseline and 12 weeks or end of study]
3. Number of Participants With a Score of 1, 2, or 3 on the Clinical Global Impression Improvement Scale [12 weeks]
4. Immune Marker IL-2 [Baseline and 12 weeks or end of study]
5. Immune Marker IL-4 [Baseline and12 weeks or end of study]
6. Immune Marker IL-6 [Changes from Baseline in Immune markers at 12 weeks or end of study]
7. Immune Marker IFN-Y (Gamma) [Baseline and 12 weeks or end of study]
8. Immune Marker Hs-CRP (High Sensitivity C Reactive Protein) [Baseline and 12 weeks or end of study]
9. Immune Marker S-100B [Baseline and 12 weeks or end of treatment]
Other Outcome Measures
1. Vital Signs - Weight [Baseline and 12 weeks or end of study]
2. Vital Signs - Body Mass Index [Baseline and 12 weeks or end of study]
3. Vital Signs - Blood Pressure Systolic and Diastolic [Baseline and 12 weeks or end of study]
4. Vital Signs - Pulse [Baseline and 12 weeks or end of study]
5. Vital Signs - Temperature [Baseline and 12 weeks or end of study]
6. Laboratory Analytes [Change from Baseline in Laboratory Analytes at 12 weeks or end of study]
