Trial Outcomes & Findings for Withania Somnifera: an Immunomodulator and Anti-inflammatory Agent for Schizophrenia (NCT NCT01793935)

NCT ID: NCT01793935

Last Updated: 2018-01-03

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 68 participants
• Primary outcome timeframe: Baseline and 12 Weeks
• Results posted on: 2018-01-03

Participant Flow

Participant milestones

Measure	Sensoril® Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo Placebo 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.
Overall Study STARTED	34	34
Overall Study COMPLETED	28	31
Overall Study NOT COMPLETED	6	3

Reasons for withdrawal

Measure	Sensoril® Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo Placebo 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.
Overall Study Pregnancy	1	0
Overall Study Protocol Violation	2	1
Overall Study Adverse Event	2	0
Overall Study Patient did not take study medication	1	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Withania Somnifera: an Immunomodulator and Anti-inflammatory Agent for Schizophrenia

Baseline characteristics by cohort

Measure	Sensoril® n=34 Participants Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo n=34 Participants Placebo 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.	Total n=68 Participants Total of all reporting groups
Age, Continuous	45.18 years STANDARD_DEVIATION 12.90 • n=5 Participants	47.38 years STANDARD_DEVIATION 11.37 • n=7 Participants	46.28 years STANDARD_DEVIATION 12.12 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	20 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	14 Participants n=7 Participants	35 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	22 Participants n=5 Participants	14 Participants n=7 Participants	36 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	20 Participants n=7 Participants	32 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	34 Participants n=5 Participants	34 Participants n=7 Participants	68 Participants n=5 Participants
Diagnosis Schizophrenia or Schizoaffective Diagnosis Schizophrenia	21 Participants n=5 Participants	18 Participants n=7 Participants	39 Participants n=5 Participants
Diagnosis Schizophrenia or Schizoaffective Diagnosis Schizoaffective	13 Participants n=5 Participants	16 Participants n=7 Participants	29 Participants n=5 Participants
Number of lifetime psychiatric hospitalizations	7.71 psychiatric hospitalizations STANDARD_DEVIATION 6.45 • n=5 Participants	7.76 psychiatric hospitalizations STANDARD_DEVIATION 6.90 • n=7 Participants	7.74 psychiatric hospitalizations STANDARD_DEVIATION 6.63 • n=5 Participants
Age at onset of 1st episode	24.32 years STANDARD_DEVIATION 10.89 • n=5 Participants	24.00 years STANDARD_DEVIATION 7.67 • n=7 Participants	24.16 years STANDARD_DEVIATION 9.35 • n=5 Participants
Current Smokers	22 Participants n=5 Participants	19 Participants n=7 Participants	41 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 12 Weeks

Population: 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes

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

Outcome measures

Measure	Sensoril® n=33 Participants Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo n=33 Participants Placebo 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.
Positive and Negative Syndrome Scale (PANSS) PANSS Positive Baseline	19.58 units on a scale Standard Deviation 3.34	19.97 units on a scale Standard Deviation 2.57
Positive and Negative Syndrome Scale (PANSS) PANSS Positive at 12 weeks	14.39 units on a scale Standard Deviation 3.94	15.33 units on a scale Standard Deviation 4.75
Positive and Negative Syndrome Scale (PANSS) PANSS Negative Baselin	16.52 units on a scale Standard Deviation 4.52	17.27 units on a scale Standard Deviation 5.25
Positive and Negative Syndrome Scale (PANSS) PANSS Negative at 12 weeks	12.97 units on a scale Standard Deviation 4.46	15.88 units on a scale Standard Deviation 5.75
Positive and Negative Syndrome Scale (PANSS) PANSS General Baseline	33.79 units on a scale Standard Deviation 5.04	33.24 units on a scale Standard Deviation 5.27
Positive and Negative Syndrome Scale (PANSS) PANSS General at 12 weeks	26.55 units on a scale Standard Deviation 4.99	30.27 units on a scale Standard Deviation 7.45
Positive and Negative Syndrome Scale (PANSS) PANSS Total at Baseline	69.88 units on a scale Standard Deviation 8.00	69.48 units on a scale Standard Deviation 8.45
Positive and Negative Syndrome Scale (PANSS) PANSS total at 12 weeks	53.91 units on a scale Standard Deviation 11.40	61.48 units on a scale Standard Deviation 14.89

SECONDARY outcome

Timeframe: Baseline and 12 weeks or end of treatment

Population: 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes

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,

Outcome measures

Measure	Sensoril® n=33 Participants Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo n=33 Participants Placebo 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.
Perceived Stress Scale (PSS) PSS score at Baseline	22.48 units on a scale Standard Deviation 7.27	20.55 units on a scale Standard Deviation 6.68
Perceived Stress Scale (PSS) PSS score at 12 weeks	14.67 units on a scale Standard Deviation 5.87	18.09 units on a scale Standard Deviation 6.64

SECONDARY outcome

Timeframe: Baseline and 12 weeks or end of study

Population: 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes

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

Outcome measures

Measure	Sensoril® n=33 Participants Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo n=33 Participants Placebo 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.
Clinical Global Impression Scale (CGI-S) - Severity CGI Severity score at baseline	4.06 units on a scale Standard Deviation 0.24	4.09 units on a scale Standard Deviation 0.38
Clinical Global Impression Scale (CGI-S) - Severity CGI Severity score at 12 weeks	3.88 units on a scale Standard Deviation 0.49	3.97 units on a scale Standard Deviation 0.47

SECONDARY outcome

Timeframe: 12 weeks

Population: 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes

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

Outcome measures

Measure	Sensoril® n=33 Participants Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo n=33 Participants Placebo 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.
Number of Participants With a Score of 1, 2, or 3 on the Clinical Global Impression Improvement Scale	12 Participants	8 Participants

SECONDARY outcome

Timeframe: Baseline and 12 weeks or end of study

Population: IL-2 levels undetectable.

Changes in immune marker IL-2 will be assessed in response to study medication.

Outcome measures

Measure	Sensoril® n=33 Participants Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo n=33 Participants Placebo 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.
Immune Marker IL-2	NA pg/mL Standard Deviation NA data cannot be summarized- IL-2 levels undetectable	NA pg/mL Standard Deviation NA data cannot be summarized- IL-2 levels undetectable

SECONDARY outcome

Timeframe: Baseline and12 weeks or end of study

Population: Data cannot be summarized- IL-4 levels undetectable

Changes in immune marker IL-4 will be assessed in response to study medication.

Outcome measures

Measure	Sensoril® n=33 Participants Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo n=33 Participants Placebo 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.
Immune Marker IL-4	NA pg/mL Standard Deviation NA data cannot be summarized- IL-4 levels undetectable	NA pg/mL Standard Deviation NA data cannot be summarized- IL-4 levels undetectable

SECONDARY outcome

Timeframe: Changes from Baseline in Immune markers at 12 weeks or end of study

Population: The "number analyzed" differs from the "overall number of participants analyzed" because not all participants had baseline and end of treatment values for IL-6.

Changes in immune marker IL-6 will be assessed in response to study medication.

Outcome measures

Measure	Sensoril® n=33 Participants Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo n=33 Participants Placebo 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.
Immune Marker IL-6 IL6 level at baseline	3.37 pg/mL Standard Deviation 2.53	4.29 pg/mL Standard Deviation 3.34
Immune Marker IL-6 IL 6 level at end of treatment	3.40 pg/mL Standard Deviation 2.51	3.87 pg/mL Standard Deviation 2.57

SECONDARY outcome

Timeframe: Baseline and 12 weeks or end of study

Population: data cannot be summarized IFN-Y (gamma) levels undetectable

Changes in immune marker IFN-Y (gamma) will be assessed in response to study medication.

Outcome measures

Measure	Sensoril® n=33 Participants Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo n=33 Participants Placebo 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.
Immune Marker IFN-Y (Gamma)	NA pg/mL Standard Deviation NA data cannot be summarized IFN-Y (gamma) levels undetectable	NA pg/mL Standard Deviation NA data cannot be summarized IFN-Y (gamma) levels undetectable

SECONDARY outcome

Timeframe: Baseline and 12 weeks or end of study

Population: The "number analyzed" differs from the "overall number of participants analyzed" because not all participants had baseline and end of treatment values for hs-CRP.

Changes in immune marker hs-CRP (high sensitivity C Reactive Protein) will be assessed in response to study medication.

hsCRP - mg/L

Outcome measures

Measure	Sensoril® n=33 Participants Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo n=33 Participants Placebo 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.
Immune Marker Hs-CRP (High Sensitivity C Reactive Protein) Pre Rx	5.57 mg/L Standard Deviation 8.57	6.27 mg/L Standard Deviation 6.90
Immune Marker Hs-CRP (High Sensitivity C Reactive Protein) End of Rx	4.49 mg/L Standard Deviation 5.09	7.82 mg/L Standard Deviation 8.25

SECONDARY outcome

Timeframe: Baseline and 12 weeks or end of treatment

Population: The "number analyzed" differs from the "overall number of participants analyzed" because not all participants had baseline and end of treatment values for 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

Outcome measures

Measure	Sensoril® n=33 Participants Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo n=33 Participants Placebo 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.
Immune Marker S-100B S100B pre Rx	39.36 pg/mL Standard Deviation 89.92	34.95 pg/mL Standard Deviation 56.12
Immune Marker S-100B S100B end of Rx	26.38 pg/mL Standard Deviation 79.44	62.49 pg/mL Standard Deviation 173.92

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and 12 weeks or end of study

Population: 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes

Clinically significant changes in weight will be assessed for "normal" or "abnormal" following randomization to 12 weeks or end of study

Outcome measures

Measure	Sensoril® n=33 Participants Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo n=33 Participants Placebo 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.
Vital Signs - Weight Body Weight at baseline	194.61 lbs Standard Deviation 49.57	191.33 lbs Standard Deviation 41.29
Vital Signs - Weight Body Weight at end of Rx	197.00 lbs Standard Deviation 51.94	193.06 lbs Standard Deviation 41.33

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and 12 weeks or end of study

Population: 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes

Clinically significant changes in BMI will be assessed for "normal" or "abnormal" following randomization to 12 weeks or end of study.

Outcome measures

Measure	Sensoril® n=33 Participants Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo n=33 Participants Placebo 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.
Vital Signs - Body Mass Index BMI at baseline	30.00 kg/m^2 Standard Deviation 7.56	30.36 kg/m^2 Standard Deviation 6.35
Vital Signs - Body Mass Index BMI at end of treatment	30.33 kg/m^2 Standard Deviation 8.04	30.56 kg/m^2 Standard Deviation 6.24

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and 12 weeks or end of study

Population: 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes

Clinically significant changes in BP will be assessed for "normal" or "abnormal" following randomization to 12 weeks or end of study.

Outcome measures

Measure	Sensoril® n=33 Participants Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo n=33 Participants Placebo 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.
Vital Signs - Blood Pressure Systolic and Diastolic Systolic BP at baseline	124.67 mm/Hg Standard Deviation 10.53	123.42 mm/Hg Standard Deviation 15.32
Vital Signs - Blood Pressure Systolic and Diastolic Systolic BP at end of treatment	123.36 mm/Hg Standard Deviation 9.30	118.39 mm/Hg Standard Deviation 23.19
Vital Signs - Blood Pressure Systolic and Diastolic Diastolic BP at baseline	79.15 mm/Hg Standard Deviation 7.95	76.52 mm/Hg Standard Deviation 11.52
Vital Signs - Blood Pressure Systolic and Diastolic Diastolic BP at end of treatment	79.06 mm/Hg Standard Deviation 7.31	75.55 mm/Hg Standard Deviation 13.21

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and 12 weeks or end of study

Population: 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes

Clinically significant changes in Pulse will be assessed for "normal" or "abnormal" following randomization to 12 weeks or end of study.

Outcome measures

Measure	Sensoril® n=33 Participants Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo n=33 Participants Placebo 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.
Vital Signs - Pulse Pulse at baseline	76.18 beats/min Standard Deviation 13.38	74.91 beats/min Standard Deviation 11.75
Vital Signs - Pulse Pulse at end of treatment	75.42 beats/min Standard Deviation 14.64	76.42 beats/min Standard Deviation 9.56

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and 12 weeks or end of study

Population: 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes

Clinically significant changes in Temperature will be assessed for "normal" or "abnormal" following randomization to 12 weeks or end of study.

Outcome measures

Measure	Sensoril® n=33 Participants Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo n=33 Participants Placebo 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.
Vital Signs - Temperature Temperature at baseline	97.38 degrees F Standard Deviation 0.57	97.36 degrees F Standard Deviation 0.72
Vital Signs - Temperature Temperature at end of treatment	97.37 degrees F Standard Deviation 0.73	97.31 degrees F Standard Deviation 0.46

OTHER_PRE_SPECIFIED outcome

Timeframe: Change from Baseline in Laboratory Analytes at 12 weeks or end of study

Changes in laboratory analytes will be classified as "normal" or "abnormal" (example: white blood cell counts)

Outcome measures

Outcome data not reported

Adverse Events

Sensoril®

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Sensoril® n=33 participants at risk Sensoril® is a proprietary extract of Withania Somnifera Sensoril®: Sensoril® is a proprietary extract of Withania Somnifera. Each Sensoril® capsules will contain 250 mg of standardized extract of Withania Somnifera	Placebo n=33 participants at risk Placebo 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.
Gastrointestinal disorders loose stools/diarrhea	18.2% 6/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes	15.2% 5/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes
Gastrointestinal disorders dry mouth	6.1% 2/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes	0.00% 0/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes
Gastrointestinal disorders nausea	6.1% 2/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes	0.00% 0/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes
Gastrointestinal disorders dyspepsia (heartburn)	9.1% 3/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes	9.1% 3/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes
Gastrointestinal disorders epigastric discomfort	9.1% 3/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes	6.1% 2/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes
Psychiatric disorders anxiety	0.00% 0/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes	6.1% 2/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes
Psychiatric disorders hyperactive	6.1% 2/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes	0.00% 0/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes
Psychiatric disorders confusion	0.00% 0/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes	6.1% 2/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes
Psychiatric disorders worsening of psychiatric symptoms	6.1% 2/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes	3.0% 1/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes
Nervous system disorders somnolence	21.2% 7/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes	9.1% 3/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes
Nervous system disorders headache	6.1% 2/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes	12.1% 4/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes
General disorders fatigue/lathargy	6.1% 2/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes	6.1% 2/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes
Skin and subcutaneous tissue disorders rash	6.1% 2/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes	0.00% 0/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes
Metabolism and nutrition disorders weight gain	6.1% 2/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes	3.0% 1/33 • Adverse Events were evaluated during the study period (12 weeks) 34 subjects were randomized to each treatment group, but 1 subject in each group did not return to pick up study medication and therefore were not included in the Intention-to-Treat (ITT) sample for analysis of outcomes

Additional Information

Dr. K.N. Roy Chengappa - PI

University of Pittsburgh

Phone: 412-246-5006

Email: chengappakn@upmc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place