| CTRI Number |
CTRI/2025/10/095887 [Registered on: 10/10/2025] Trial Registered Prospectively |
| Last Modified On: |
09/10/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug
Nutraceutical |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
Mitophagy-targeted Intervention for Negative symptoms and cognitive Deficits in Schizophrenia with Urolithin A |
|
Scientific Title of Study
|
A double- blind randomised placebo-controlled trial of Urolithin-A for deficit symptoms in Schizophrenia: focus on dysfunctional mitophagy |
| Trial Acronym |
MIND-UA |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
SREERAJ VS |
| Designation |
Associate professor of Psychiatry |
| Affiliation |
National Institute of Mental Health and Neuro Sciences (NIMHANS) |
| Address |
Department of Psychiatry
National Institute of Mental Health and Neuro Sciences (NIMHANS), BENGALURU-560029
Bangalore
KARNATAKA
560029
India |
| Phone |
08026995825 |
| Fax |
|
| Email |
vs8sreeraj@yahoo.com |
|
Details of Contact Person
Scientific Query
|
| Name |
SREERAJ VS |
| Designation |
Associate professor of Psychiatry |
| Affiliation |
National Institute of Mental Health and Neuro Sciences (NIMHANS) |
| Address |
Department of Psychiatry
National Institute of Mental Health and Neuro Sciences (NIMHANS), BENGALURU-560029
Bangalore
KARNATAKA
560029
India |
| Phone |
08026995825 |
| Fax |
|
| Email |
vs8sreeraj@yahoo.com |
|
Details of Contact Person
Public Query
|
| Name |
Shivakumar V |
| Designation |
Scientist-E |
| Affiliation |
National Institute of Mental Health and Neuro Sciences (NIMHANS) |
| Address |
Department of Integrative Medicine
National Institute of Mental Health and Neuro Sciences (NIMHANS), BENGALURU-560029
Bangalore
KARNATAKA
560029
India |
| Phone |
08026972083 |
| Fax |
|
| Email |
drshiv.nimhans@gmail.com |
|
|
Source of Monetary or Material Support
|
| Indian Council of medical reserach (ICMR), V. Ramalingaswami Bhawan, P.O. Box No. 4911, Ansari Nagar, New Delhi - 110029, India |
|
|
Primary Sponsor
|
| Name |
Department of Psychiatry National Institute of Mental Health and Neuro Sciences (NIMHANS) |
| Address |
Department of Psychiatry National Institute of Mental Health and Neuro Sciences (NIMHANS), Hosur Road Bengaluru-560029 Karnataka India
|
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr SREERAJ VS |
National Institute of Mental Health and Neurosciences |
Department of Psychiatry
NIMHANS, BENGALURU
Bangalore
KARNATAKA |
08026995825
vs8sreeraj@yahoo.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| NIMHANS ETHICS COMMITTEE - BEHAVIOURAL SCIENCES |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: F20-F29||Schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Placebo |
Two capsules per day for 90 days |
| Intervention |
Urolithin A |
500mg two capsules per day for 90 days |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
50.00 Year(s) |
| Gender |
Both |
| Details |
a.18-50 years both sexes
b. A minimum education level of 8th grade
c. Schizophrenia and related disorders as per the diagnostic and statistical manual of mental
disorders (DSM5)
d. On stable antipsychotic dose for minimum 4 weeks with persistent deficit symptoms
defined based on MoCA+DSST and/or SANS (defined below)
e. Providing written informed consent |
|
| ExclusionCriteria |
| Details |
a. Patients with prominent psychotic symptoms [Global item of Scale for Assessment of
Positive Symptoms >3 59 ].
b. Patients with any co-morbid neurological/medical disorder, or intellectual disability
disorder to the severity that impedes the trial participation
c. Current psychoactive substance dependence (except caffeine or nicotine)
d. Suicidal risk or psychiatric emergency
e. Pregnancy/post-partum period |
|
|
Method of Generating Random Sequence
|
Permuted block randomization, variable |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Participant and Outcome Assessor Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Change in Negative symptoms (Scale for assessment of Negative symptoms) score and Cognitive deficits (Brief Assessment of Cognition in Schizophrenia) composite score |
from baseline to 3 months of the intervention |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Change in SANS score and BACS composite score |
from baseline to 1 and 2 months of the intervention |
Change in other clinical measures (CAINS, SAPS, BPRS, GAF, GSDS, CGI, MedDRA
events and subdomains of BACS) |
from baseline to 1, 2 and 3 months of the intervention |
| Urolithin levels |
from baseline to 3 months of the intervention |
| Mitophagy markers, mitochondrial bioenergetics, membrane potentials and Brain MRS markers |
from baseline to 3 months of the intervention |
|
|
Target Sample Size
|
Total Sample Size="80"
Sample Size from India="80"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3/ Phase 4 |
|
Date of First Enrollment (India)
|
01/02/2026 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="5"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Yet Recruiting |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - YES
- What data in particular will be shared?
Response (Others) - The respective individual participant data reported in each of the potential series of publications will be available for sharing with researchers as per the national / international guidelines; further details about accessing this data is provided in the responses below.
- What additional supporting information will be shared?
Response - Study Protocol
Response - Statistical Analysis Plan
Response (Others) - Other supporting information recommended by the national / international guidelines
- Who will be able to view these files?
Response (Others) - - The prospective researcher who intends to access the data will be required to submit an application to the principal investigator providing certain details (ex. type of data requested, summary of planned research and related information). An expert committee will assess whether the proposed use of the dataset is scientifically and ethically appropriate and to ensure that there are no potential scientific or other conflicts of interest. Those researchers that are permitted by the committee will be able to view the data.
- For what types of analyses will this data be available?
Response (Others) - The prospective researcher who intends to access the data will be required to submit an application to the principal investigator providing certain details (ex. type of data requested, summary of planned research and related information). An expert will assess whether the proposed use of the dataset is scientifically and ethically appropriate and to ensure that there are no potential scientific or other conflicts of interest. The data will be available for those proposed analyses that are approved by the committee.
- By what mechanism will data be made available?
Response (Others) - The prospective researcher who intends to access the data will be required to submit an application to the principal investigator providing certain details (ex. type of data requested, summary of planned research and related information). An expert will assess whether the proposed use of the dataset is scientifically and ethically appropriate and to ensure that there are no potential scientific or other conflicts of interest. The data will be available for those proposed analyses that are approved by the committee. The data will be made available through web interface.
- For how long will this data be available start date provided 02-01-1970 and end date provided 02-01-1970?
Response - Beginning 9 months and ending 36 months following article publication.
- Any URL or additional information regarding plan/policy for sharing IPD?
Additional Information - NIL
|
|
Brief Summary
|
Rationale: Schizophrenia affects 10% of India’s population and is a major cause of psychiatric disability. Deficit symptoms, the core cause of disability, are linked to neuroinflammation and oxidative stress. Mitochondrial dysfunction, primarily with impaired mitophagy (self-clearance of damaged mitochondria), leads to cellular dysfunction, energy dysregulation, and inflammation. Therapies targeting mitophagy could address the core pathology. Urolithin A (UA), derived from dietary ellagitannins via gut microbiota, enhances mitophagy and lysosomal health.
Objectives: Evaluate the clinical efficacy of UA supplementation versus placebo in improving deficit symptoms in schizophrenia. To identify theranostic and mechanistic mitochondrial markers of the adjunct UA, in schizophrenia, in-vitro and in-vivo. Methods: In this placebo-controlled trial, 40 of the 80 patients will be randomized to receive 500mg of oral supplementation of UA for three months. Clinical and cognitive outcomes will be assessed along with the blood and brain-magnetic resonance spectroscopy-based mitochondrial markers. Similar data from 40 healthy volunteers will be used to validate biomarkers. The mechanism of UA-mediated mitophagy will be assessed with in-vivo exposures in a subset of participants’ lymphoblastoid cell lines (LCLs) derived from the peripheral blood mononuclear cells (PBMCs).
Expected outcome: This high-risk, high-reward study offers a novel approach to managing deficit symptoms. Its mechanistic and theranostic insights could identify responders early and guide the development of low-cost interventions like dietary ellagitannins and specific UA-synthesising probiotics. |