Sensoril(Ashwaganhda)for Bipolar Disorder

Sensoril® (Ashwagandha) - A Standardized Extract From a Medicinal Plant - (Withania Somnifera) for Cognitive Enhancement in Persons With Bipolar Disorder: A Parallel Group, Randomized Double Blind, and Placebo Controlled Study

The investigators hypothesis is that oral Sensoril® (as compared to placebo) will enhance cognitive abilities (specifically measures of attention, executive function, working memory, and visuospatial ability) in persons with bipolar disorder. Secondarily, the investigators hypothesize there will be secondary improvements in residual mood/anxiety symptoms, and metabolic indices, if impaired (fasting blood glucose and lipids).

The investigators aim to test these hypotheses by conducting a randomized, placebo controlled, add on treatment trial of Sensoril® (added to existing mood stabilizer treatment) recruiting 60 subjects with DSM IV-TR bipolar disorder for a period of 8 weeks. Measures of cognition, psychopathology and laboratory indices will be utilized for evaluating primary and secondary outcomes, along with safety assessments.

Study Overview

• Status: Completed
• Conditions: Bipolar I Disorder; Bipolar II Disorder; Bipolar Disorder NOS
• Intervention / Treatment: Other: Placebo; Drug: Sensoril

Detailed Description

OBJECTIVE:

To evaluate if Sensoril® treatment of persons with bipolar illness will improve their cognitive performance and if it will improve residual mood/anxiety symptoms and impaired metabolic indices.

RESEARCH PLAN:

We will conduct a randomized, placebo controlled, add on treatment trial of Sensoril® (added to ongoing prescribed pharmacological mood stabilizer) for a period of 8 weeks. Measures of cognition, psychopathology and laboratory indices will be utilized for evaluating primary and secondary outcomes, along with safety assessments.

METHODS:

Up to Seventy-six subjects with DSM IV bipolar I disorder will be recruited from Western Psychiatric Institute and Clinic. Using a 1:1 randomization, subjects who sign an informed consent document will be randomized to receive Sensoril® or placebo.

It is expected that 16 of the 76 subjects may not meet inclusion/exclusion criteria, leaving 60 consenting adults (18 to 65 years) with DSM IV-TR Bipolar Disorder who will be assessed for euthymia (Young Mania Rating Scale Score of less than or equal to 10, Montgomery Asberg Depression Rating Scale Score of less than or equal to 10) over the period of 4 weeks while receiving stable doses of their current mood stabilizer. They will also be assessed for cognitive dysfunction (attention/executive function, immediate and declarative memory, psychomotor performance) using Cogtest - a proprietary neuropsychological battery of tests. These subjects will be characterized for normal pre-morbid IQ, no ECT treatment in past 6 months, no alcohol or substance dependence in past 6 months, mini-mental state score of 23 or more.

Sensoril® (or placebo) will be administered using random assignment at a dose of 250mg/day, increasing to a dose of 500mg/day by the second week. The dose of 500mg (or 250mg if tolerability is an issue) will be continued fora total of 8 weeks. Sensoril® is not known to have interactions with psychotropic drugs, but mood-stabilizer levels will be monitored at the beginning and end of the study. The principal investigator has worked with a New Jersey based company (Natreon, Inc.) to obtain an IND from the FDA for Sensoril® treatment of cognitive dysfunction in persons with Bipolar disorder (IND #102616).

Standard psychopathology rating scales will be administered to evaluate impact if any on residual symptoms of bipolar disorder. Laboratory indices (glucose/lipids) will be evaluated at baseline and end of study. Safety will be assessed through a comprehensive health assessment, including medical history, and evaluation of laboratory measures. Any adverse effects will be assessed by asking questions at each visit, and if necessary, follow up via telephone contact or bringing subjects in for assessments outside the scheduled visits.

SIGNIFICANCE:

Cognitive dysfunction can seriously hinder improved functional outcomes in persons with bipolar disorder. If this short term intervention with Sensoril® shows promise, more definitive studies using adequate powered sample sizes, and of longer duration can be conducted. If improvements in cognitive problems are linked to improved functional outcomes using such supplemental treatments, an important therapeutic milestone in bipolar disorder will have been achieved.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Western Psychiatric Institute and Clinic
    • Pittsburgh, Pennsylvania, United States, 15213-2593
      • Western Psychiatric Institute and Clinic University of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• DSMIV-TR diagnosis of Bipolar Disorder
• Ages 18 to 65
• Men or Women
• 8th grade education or greater
• Able to provide competent written informed consent
• Current main mood stabilizer and mood status (YMRS and MADRS scores less than or equal to 10) are stable for greater than or equal to 4 weeks by history.

Exclusion Criteria:

• Medically unstable conditions
• Known allergy to Sensoril® (or Ashwagandha)
• Current cognitive decline is attributable to a diagnosis of dementia or other neurological disorder
• Pregnant or lactating women
• Mini-mental score (MMSE) less than or equal to 23
• Currently receiving donepezil, rivastigamine, or galatamine, or memantine or any marketed agent for slowing memory loss in dementia
• Abnormal clinical thyroid status
• Currently (or within past 2 weeks) receiving St. John's Wort, Gingko or Omega-3

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1- Sensoril (Ashwagandha); Sensoril (Ashwagandha) will be administered using random assignment at a dose of 250 mg/day, increasing to a dose of 500 mg/day by the second week.	Drug: Sensoril; Other Names: Ashwagandha
Placebo Comparator: 2 - Placebo; Placebo will be administered using random assignment at a dose of 250 mg/day, increasing to a dose of 500 mg/day by the second week.	Other: Placebo; Other Names: Sugar Pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Digit-Span Score at 8 Weeks	Cognition was assessed using tests developed by The Cognition Group-(TCG); London, UK; and Delaware, USA. Testing procedures and consistency was assured by the same staff-patient dyad, and a TCG staff person had previously trained the research staff (Chengappa et al, 2012). A comprehensive cognitive battery was assessed. Details of these cognitive tests are available at http://www.cogtest.com, and are also described in other studies (Harvey et al, 2007, Lindenmayer et al, 2011, Chengappa et al, 2012). However, the results for Digit span which assesses short term or working memory are presented. The raw scores for "digit span" ranges from a minimum of 2 to a maximum of 8. The Digit Span test measures working memory and the longer the span the better the cognition therefore the higher score is the better outcome.	8 week treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensoril® Treatment Will Secondarily Improve Any Residual Depressive Symptoms	Depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS). Minimum score = 0, Maximum score = 60. Higher scores on MADRS indicate worse functioning.	Baseline and 8 week treatment
Sensoril Treatment Will Secondarily Improve Any Residual Symptoms of Mania.	Manic symptoms were measured using the Young Mania Rating Scale (YMRS). Minimum score = 0, Maximum score = 60. Higher scores on YMRS indicate worse functioning.	Baseline and 8 weeks treatment
Sensoril Treatment Will Secondarily Improve Any Residual Anxiety Symptoms	Symptoms of anxiety were measured using the Hamilton Anxiety Rating Scale (HARS). Minimum score = 0, Maximum score = 60. Higher scores on HARS indicate worse functioning	Baseline and 8 week treatment

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: National Alliance for Research on Schizophrenia and Depression
• Investigators: Principal Investigator: K. N. Roy Chengappa, MD, Western Psychiatric Institute and Clinic

Publications and helpful links

General Publications

• Chengappa KN, Bowie CR, Schlicht PJ, Fleet D, Brar JS, Jindal R. Randomized placebo-controlled adjunctive study of an extract of withania somnifera for cognitive dysfunction in bipolar disorder. J Clin Psychiatry. 2013 Nov;74(11):1076-83. doi: 10.4088/JCP.13m08413.

Helpful Links

• Connect to NARSAD list of active research studies

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: September 25, 2008
• First Submitted That Met QC Criteria: September 26, 2008
• First Posted (Estimate): September 29, 2008

Study Record Updates

• Last Update Posted (Estimate): April 14, 2016
• Last Update Submitted That Met QC Criteria: March 14, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Cognitive enhancement; Bipolar Illness; Sensoril
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Bipolar and Related Disorders; Disease; Bipolar Disorder
• Other Study ID Numbers: Chengappa Sensoril; Univ.Pitts IRB# PRO08060267