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

NCT01793935 | Completed Results DMC

• 1 other identifier: SMRI #: 12T-001
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Schizophrenia; Schizoaffective Disorder

Keywords

Schizophrenia; Sensoril; Withania Somnifera extract; Total/ Positive / Negative Symptoms; Stress; Inflammation; Immunomodulation

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline and 12 Weeks

Secondary Outcomes (9)

• Perceived Stress Scale (PSS)

  Baseline and 12 weeks or end of treatment

• Clinical Global Impression Scale (CGI-S) - Severity

  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

  12 weeks

• Immune Marker IL-2

  Baseline and 12 weeks or end of study

• Immune Marker IL-4

  Baseline and12 weeks or end of study

Other Outcomes (6)

• Vital Signs - Weight

  Baseline and 12 weeks or end of study

• Vital Signs - Body Mass Index

  Baseline and 12 weeks or end of study

• Vital Signs - Blood Pressure Systolic and Diastolic

  Baseline and 12 weeks or end of study

Study Arms (2)

Sensoril®

EXPERIMENTAL

Sensoril® is a proprietary extract of Withania Somnifera

Drug: Sensoril®

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Sensoril® DRUG

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

Sensoril®

Placebo DRUG

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"

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult males or females (≥ 18 years, to 75 years)
• DSM IV TR diagnosis of schizophrenia or schizoaffective disorder (If officially instituted by study initiation: DSM V diagnoses will be used).
• Ability to provide informed written consent
• 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
• Current symptom exacerbation ≥ 2 weeks, but ≤ 1 year
• Receiving anti-psychotic medications for ≥ 4 weeks
• For women of child bearing age, a negative pregnancy test at screening.

You may not qualify if:

• Testing positive for illicit substances (marijuana or alcohol use will be assessed on a case by case basis, caffeine and nicotine are excepted)
• Receiving pharmacological treatment for addictions (naltrexone, suboxone, acamprosate, others) will be reviewed on a case by case basis
• Seriously unstable medical illnesses
• Pregnant or breast feeding women
• Known allergy or history of serious adverse event with WSE
• Subjects who may require imminent hospitalization (examples: suicidal or aggressive behavior)
• Currently receiving antibiotics, anti-viral, or anti-parasitic medications
• Currently receiving immunosuppressive medications (e.g. corticosteroids, chemotherapy or transplantation or HIV/AIDs associated drugs).
• Currently receiving NSAIDs or Aspirin (\>81 mg/day) on a daily basis or PRN use \> 2x/week (in the last 4 weeks).

Sponsors & Collaborators

• K.N. Roy Chengappa: lead

Study Sites (1)

Western Psychiatric Institute & Clinic

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Chengappa KNR, Brar JS, Gannon JM, Schlicht PJ. Adjunctive Use of a Standardized Extract of Withania somnifera (Ashwagandha) to Treat Symptom Exacerbation in Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study. J Clin Psychiatry. 2018 Jul 10;79(5):17m11826. doi: 10.4088/JCP.17m11826.

  PMID: 29995356 DERIVED

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Inflammation

Interventions

Ashwagandha; Sugars

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carbohydrates

Results Point of Contact

• Title: Dr. K.N. Roy Chengappa - PI
• Organization: University of Pittsburgh

chengappakn@upmc.edu

412-246-5006

Study Officials

• KN Roy Chengappa, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: February 12, 2013
• First Posted: February 18, 2013
• Study Start: April 1, 2013
• Primary Completion: July 7, 2016
• Study Completion: July 7, 2016
• Last Updated: January 3, 2018
• Results First Posted: November 22, 2017

Record last verified: 2017-10

Locations

US (1)