An interventional study of Sensoril® and Placebo in Schizophrenia and Schizoaffective Disorder, sponsored by K.N. Roy Chengappa. Completed at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2018-01-03.
Sponsored by K.N. Roy Chengappa · Not applicable, Interventional, and Treatment
Withania somnifera (WSE; Ashwagandha in Ayurveda) extracts have been used as an adaptogen or to build resistance to stress or diseases in indigenous medical systems in India for centuries. Modern scientific data for WSE indicate several bioactive molecules (withanolides, withanosides, indosides, withaferin-A, others) with significant immunomodulatory, anti-inflammatory and stress reducing properties.
This study will examine whether a standardized extract of Withania Somnifera (WSE; Sensoril®) will improve total, positive, negative symptoms, and stress in patients with schizophrenia. The study will examine whether WSE reduces PANSS positive and negative symptoms and stress scores in subjects, and whether these improvements are mediated by changes in inflammatory immune indices. An additional aim will determine if patients receiving WSE will have fewer adjustments to their psychotropic medications that those assigned to placebo. The study will examine whether WSE will re-balance Th1/Th2 ratios (cytokine measures) and mediate a reduction of elevated hs-CRP levels. It is hypothesized that those subjects whose Th1/Th2 ratios normalize will likely have a greater magnitude of clinical improvement versus those subjects whose immune ratios remain unbalanced.
The proposal is a 12-week, double-blind, placebo-controlled RCT of WSE added to antipsychotic medications in approximately 60 or more patients with schizophrenia with an exacerbation of symptoms. If efficacy is affirmed, this low cost extract could be studied further, and used quite readily across low, middle and high income countries.
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.
3,471 studies on the registry are indexed under Schizophrenia; 472 are open to participants now.
This study's enrollment of 68 is close to the median of 70 across 2,872 interventional studies indexed under Schizophrenia.
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Sensoril® is a proprietary extract of Withania Somnifera
Drug: Sensoril®
Placebo
Drug: Placebo
Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera
Also known as: Ashwagandha
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.
Also known as: "Sugar Pill"
Positive and Negative Syndrome Scale (PANSS)
The Positive and Negative Syndrome Scale (PANSS) measures symptom severity in patients with psychotic illnesses. It yields a total score as well as subscores for Positive symptoms, Negative symptoms and General symptoms. PANSS Positive subscale consists of 7 Items - (minimum score = 7, maximum score = 49) - Higher values represent a worse outcome. PANSS Negative subscale consists of 7 Items - (minimum score = 7, maximum score = 49) - Higher values represent a worse outcome. General Psychopathology subscale consists of 16 items - (minimum score = 16, maximum score = 112) - Higher values represent a worse outcome. PANSS Total Score - The 3 subscales scores are summed to compute a PANSS Total score. The minimum PANSS total score = 30, maximum = 210 - Higher values represent a worse outcome
Time frame: Baseline and 12 Weeks
Perceived Stress Scale (PSS)
The Perceived Stress Scale (PSS) was developed to measure the degree to which situations in one's life are appraised as stressful. Perceived Stress Scale Scoring Each item is rated on a 5-point scale ranging from never (0) to very often (4). Positively worded items are reverse scored, and the ratings are summed, with higher scores indicating more perceived stress. PSS-10 scores are obtained by reversing the scores on the four positive items: For example, 0=4, 1=3, 2=2, etc. and then summing across all 10 items. Items 4, 5, 7, and 8 are the positively stated items. Total score can range from 0 to 40. Scores around 13 are considered average. Scores of 20 or higher are considered high stress,
Time frame: Baseline and 12 weeks or end of treatment
Clinical Global Impression Scale (CGI-S) - Severity
The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Possible ratings are: 0 = not assessed, 1 = Normal, not at all ill, 2 = Borderline mentally ill, 3 = Mildly ill, 4 = Moderately ill, 5 = Markedly ill, 6 = Severely ill, 7 = Among the most extremely ill patients - The higher the score the worse outcome
Time frame: Baseline and 12 weeks or end of study
Number of Participants With a Score of 1, 2, or 3 on the Clinical Global Impression Improvement Scale
The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: Possible ratings are: 1= Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5= Minimally worse, 6= Much worse, 7=Very much worse. The higher the score the worse outcome
Time frame: 12 weeks
Immune Marker IL-2
Changes in immune marker IL-2 will be assessed in response to study medication.
Time frame: Baseline and 12 weeks or end of study
Immune Marker IL-4
Changes in immune marker IL-4 will be assessed in response to study medication.
Time frame: Baseline and12 weeks or end of study
Immune Marker IL-6
Changes in immune marker IL-6 will be assessed in response to study medication.
Time frame: Changes from Baseline in Immune markers at 12 weeks or end of study
Immune Marker IFN-Y (Gamma)
Changes in immune marker IFN-Y (gamma) will be assessed in response to study medication.
Time frame: Baseline and 12 weeks or end of study
Immune Marker Hs-CRP (High Sensitivity C Reactive Protein)
Changes in immune marker hs-CRP (high sensitivity C Reactive Protein) will be assessed in response to study medication. hsCRP - mg/L
Time frame: Baseline and 12 weeks or end of study
Immune Marker S-100B
Changes in immune marker S-100B will be assessed in response to study medication. Elisa * Sensitivity 2.7 picogm/ml * Range 2.7 to 2000 picogm/ml
Time frame: Baseline and 12 weeks or end of treatment
Vital Signs - Weight
Clinically significant changes in weight will be assessed for "normal" or "abnormal" following randomization to 12 weeks or end of study
Time frame: Baseline and 12 weeks or end of study
Vital Signs - Body Mass Index
Clinically significant changes in BMI will be assessed for "normal" or "abnormal" following randomization to 12 weeks or end of study.
Time frame: Baseline and 12 weeks or end of study
Vital Signs - Blood Pressure Systolic and Diastolic
Clinically significant changes in BP will be assessed for "normal" or "abnormal" following randomization to 12 weeks or end of study.
Time frame: Baseline and 12 weeks or end of study
Vital Signs - Pulse
Clinically significant changes in Pulse will be assessed for "normal" or "abnormal" following randomization to 12 weeks or end of study.
Time frame: Baseline and 12 weeks or end of study
Vital Signs - Temperature
Clinically significant changes in Temperature will be assessed for "normal" or "abnormal" following randomization to 12 weeks or end of study.
Time frame: Baseline and 12 weeks or end of study
Laboratory Analytes
Changes in laboratory analytes will be classified as "normal" or "abnormal" (example: white blood cell counts)
Time frame: Change from Baseline in Laboratory Analytes at 12 weeks or end of study
| Milestone | Sensoril® | Placebo |
|---|---|---|
| Started | 34 | 34 |
| Completed | 28 | 31 |
| Not completed | 6 | 3 |
| Withdrew: Pregnancy | 1 | 0 |
| Withdrew: Protocol violation | 2 | 1 |
| Withdrew: Adverse event | 2 | 0 |
| Withdrew: Patient did not take study medication | 1 | 1 |
| Withdrew: Lost to follow-up | 0 | 1 |
The Positive and Negative Syndrome Scale (PANSS) measures symptom severity in patients with psychotic illnesses. It yields a total score as well as subscores for Positive symptoms, Negative symptoms and General symptoms. PANSS Positive subscale consists of 7 Items - (minimum score = 7, maximum score = 49) - Higher values represent a worse outcome. PANSS Negative subscale consists of 7 Items - (minimum score = 7, maximum score = 49) - Higher values represent a worse outcome. General Psychopathology subscale consists of 16 items - (minimum score = 16, maximum score = 112) - Higher values represent a worse outcome. PANSS Total Score - The 3 subscales scores are summed to compute a PANSS Total score. The minimum PANSS total score = 30, maximum = 210 - Higher values represent a worse outcome
| units on a scale | Sensoril® | Placebo |
|---|---|---|
| PANSS Positive Baseline | 19.58 ± 3.34 | 19.97 ± 2.57 |
| PANSS Positive at 12 weeks | 14.39 ± 3.94 | 15.33 ± 4.75 |
| PANSS Negative Baselin | 16.52 ± 4.52 | 17.27 ± 5.25 |
| PANSS Negative at 12 weeks | 12.97 ± 4.46 | 15.88 ± 5.75 |
| PANSS General Baseline | 33.79 ± 5.04 | 33.24 ± 5.27 |
| PANSS General at 12 weeks | 26.55 ± 4.99 | 30.27 ± 7.45 |
| PANSS Total at Baseline | 69.88 ± 8.00 | 69.48 ± 8.45 |
| PANSS total at 12 weeks | 53.91 ± 11.40 | 61.48 ± 14.89 |
The Perceived Stress Scale (PSS) was developed to measure the degree to which situations in one's life are appraised as stressful. Perceived Stress Scale Scoring Each item is rated on a 5-point scale ranging from never (0) to very often (4). Positively worded items are reverse scored, and the ratings are summed, with higher scores indicating more perceived stress. PSS-10 scores are obtained by reversing the scores on the four positive items: For example, 0=4, 1=3, 2=2, etc. and then summing across all 10 items. Items 4, 5, 7, and 8 are the positively stated items. Total score can range from 0 to 40. Scores around 13 are considered average. Scores of 20 or higher are considered high stress,
| units on a scale | Sensoril® | Placebo |
|---|---|---|
| PSS score at Baseline | 22.48 ± 7.27 | 20.55 ± 6.68 |
| PSS score at 12 weeks | 14.67 ± 5.87 | 18.09 ± 6.64 |
The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Possible ratings are: 0 = not assessed, 1 = Normal, not at all ill, 2 = Borderline mentally ill, 3 = Mildly ill, 4 = Moderately ill, 5 = Markedly ill, 6 = Severely ill, 7 = Among the most extremely ill patients - The higher the score the worse outcome
| units on a scale | Sensoril® | Placebo |
|---|---|---|
| CGI Severity score at baseline | 4.06 ± 0.24 | 4.09 ± 0.38 |
| CGI Severity score at 12 weeks | 3.88 ± 0.49 | 3.97 ± 0.47 |
The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: Possible ratings are: 1= Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5= Minimally worse, 6= Much worse, 7=Very much worse. The higher the score the worse outcome
| Participants | Sensoril® | Placebo |
|---|---|---|
| Number of Participants With a Score of 1, 2, or 3 on the Clinical Global Impression Improvement Scale | 12 | 8 |
Changes in immune marker IL-2 will be assessed in response to study medication.
| pg/mL | Sensoril® | Placebo |
|---|---|---|
| Immune Marker IL-2 | NA ± NA | NA ± NA |
Changes in immune marker IL-4 will be assessed in response to study medication.
| pg/mL | Sensoril® | Placebo |
|---|---|---|
| Immune Marker IL-4 | NA ± NA | NA ± NA |
Changes in immune marker IL-6 will be assessed in response to study medication.
| pg/mL | Sensoril® | Placebo |
|---|---|---|
| IL6 level at baseline | 3.37 ± 2.53 | 4.29 ± 3.34 |
| IL 6 level at end of treatment | 3.40 ± 2.51 | 3.87 ± 2.57 |
Changes in immune marker IFN-Y (gamma) will be assessed in response to study medication.
| pg/mL | Sensoril® | Placebo |
|---|---|---|
| Immune Marker IFN-Y (Gamma) | NA ± NA | NA ± NA |
Changes in immune marker hs-CRP (high sensitivity C Reactive Protein) will be assessed in response to study medication. hsCRP - mg/L
| mg/L | Sensoril® | Placebo |
|---|---|---|
| Pre Rx | 5.57 ± 8.57 | 6.27 ± 6.90 |
| End of Rx | 4.49 ± 5.09 | 7.82 ± 8.25 |
Changes in immune marker S-100B will be assessed in response to study medication. Elisa * Sensitivity 2.7 picogm/ml * Range 2.7 to 2000 picogm/ml
| pg/mL | Sensoril® | Placebo |
|---|---|---|
| S100B pre Rx | 39.36 ± 89.92 | 34.95 ± 56.12 |
| S100B end of Rx | 26.38 ± 79.44 | 62.49 ± 173.92 |
Clinically significant changes in weight will be assessed for "normal" or "abnormal" following randomization to 12 weeks or end of study
| lbs | Sensoril® | Placebo |
|---|---|---|
| Body Weight at baseline | 194.61 ± 49.57 | 191.33 ± 41.29 |
| Body Weight at end of Rx | 197.00 ± 51.94 | 193.06 ± 41.33 |
Clinically significant changes in BMI will be assessed for "normal" or "abnormal" following randomization to 12 weeks or end of study.
| kg/m^2 | Sensoril® | Placebo |
|---|---|---|
| BMI at baseline | 30.00 ± 7.56 | 30.36 ± 6.35 |
| BMI at end of treatment | 30.33 ± 8.04 | 30.56 ± 6.24 |
Clinically significant changes in BP will be assessed for "normal" or "abnormal" following randomization to 12 weeks or end of study.
| mm/Hg | Sensoril® | Placebo |
|---|---|---|
| Systolic BP at baseline | 124.67 ± 10.53 | 123.42 ± 15.32 |
| Systolic BP at end of treatment | 123.36 ± 9.30 | 118.39 ± 23.19 |
| Diastolic BP at baseline | 79.15 ± 7.95 | 76.52 ± 11.52 |
| Diastolic BP at end of treatment | 79.06 ± 7.31 | 75.55 ± 13.21 |
Clinically significant changes in Pulse will be assessed for "normal" or "abnormal" following randomization to 12 weeks or end of study.
| beats/min | Sensoril® | Placebo |
|---|---|---|
| Pulse at baseline | 76.18 ± 13.38 | 74.91 ± 11.75 |
| Pulse at end of treatment | 75.42 ± 14.64 | 76.42 ± 9.56 |
Clinically significant changes in Temperature will be assessed for "normal" or "abnormal" following randomization to 12 weeks or end of study.
| degrees F | Sensoril® | Placebo |
|---|---|---|
| Temperature at baseline | 97.38 ± 0.57 | 97.36 ± 0.72 |
| Temperature at end of treatment | 97.37 ± 0.73 | 97.31 ± 0.46 |
Changes in laboratory analytes will be classified as "normal" or "abnormal" (example: white blood cell counts)
Results for this outcome have not been posted.
Collected over Adverse Events were evaluated during the study period (12 weeks). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Sensoril® | 0/33 (0%) | 0/33 (0%) | 24/33 (72.7%) |
| Placebo | 0/33 (0%) | 0/33 (0%) | 20/33 (60.6%) |
| Event | Sensoril® | Placebo |
|---|---|---|
| somnolenceNervous system disorders | 7/33 | 3/33 |
| loose stools/diarrheaGastrointestinal disorders | 6/33 | 5/33 |
| headacheNervous system disorders | 2/33 | 4/33 |
| dyspepsia (heartburn)Gastrointestinal disorders | 3/33 | 3/33 |
| epigastric discomfortGastrointestinal disorders | 3/33 | 2/33 |
| dry mouthGastrointestinal disorders | 2/33 | 0/33 |
| nauseaGastrointestinal disorders | 2/33 | 0/33 |
| anxietyPsychiatric disorders | 0/33 | 2/33 |
| hyperactivePsychiatric disorders | 2/33 | 0/33 |
| confusionPsychiatric disorders | 0/33 | 2/33 |
34 subjects were randomized in each group but 1 subject in each group never came to pick up study medication and therefore are not included in the Overall number of participants analyzed in each outcome measure. They did not contribute any data to the intention to treat group.
| Age, Continuous(years) | Sensoril® | Placebo | Total |
|---|---|---|---|
| Mean | 45.18 ± 12.90 | 47.38 ± 11.37 | 46.28 ± 12.12 |
| Sex: Female, Male(Participants) | Sensoril® | Placebo | Total |
|---|---|---|---|
| Female | 13 | 20 | 33 |
| Male | 21 | 14 | 35 |
| Race (NIH/OMB)(Participants) | Sensoril® | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 22 | 14 | 36 |
| White | 12 | 20 | 32 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(Participants) | Sensoril® | Placebo | Total |
|---|---|---|---|
| United States | 34 | 34 | 68 |
| Diagnosis Schizophrenia or Schizoaffective(Participants) | Sensoril® | Placebo | Total |
|---|---|---|---|
| Diagnosis Schizophrenia | 21 | 18 | 39 |
| Diagnosis Schizoaffective | 13 | 16 | 29 |
| Number of lifetime psychiatric hospitalizations(psychiatric hospitalizations) | Sensoril® | Placebo | Total |
|---|---|---|---|
| Mean | 7.71 ± 6.45 | 7.76 ± 6.90 | 7.74 ± 6.63 |
| Age at onset of 1st episode(years) | Sensoril® | Placebo | Total |
|---|---|---|---|
| Mean | 24.32 ± 10.89 | 24.00 ± 7.67 | 24.16 ± 9.35 |
| Current Smokers(Participants) | Sensoril® | Placebo | Total |
|---|---|---|---|
| Count of participants | 22 | 19 | 41 |
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K.N. Roy Chengappa