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CTRI Number  CTRI/2025/09/094902 [Registered on: 16/09/2025] Trial Registered Prospectively
Last Modified On: 15/09/2025
Post Graduate Thesis  Yes 
Type of Trial  Observational 
Type of Study   Cohort Study 
Study Design  Other 
Public Title of Study   The Gut-Brain Connection: A Study to Find Early Predictors for Patients with a Brain Bleed.  
Scientific Title of Study   Integrated Omics approach to Explore Gut Microbiome Signature, Gut integrity biomarkers and Short-chain fatty acid profile, predictive tool in Aneurysmal Subarachnoid Hemorrhage 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr HB Veenakumari 
Designation  Professor 
Affiliation  NIMHANS 
Address  Department of Neuromicrobiology National Institute of Mental Health and Neurosciences (NIMHANS) Bengaluru

Bangalore
KARNATAKA
560029
India 
Phone  9449084851  
Fax    
Email  docveenas2002@yahoo.com  
 
Details of Contact Person
Scientific Query
 
Name  Rosemary Shaji V 
Designation  Ph D Scholar 
Affiliation  NIMHANS 
Address  Department of Neuromicrobiology National Institute of Mental Health and Neurosciences (NIMHANS) Bengaluru

Bangalore
KARNATAKA
560029
India 
Phone  7025087746  
Fax    
Email  rosemaryshajiv@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Dr Dhaval Shukla 
Designation  Professor and HOD 
Affiliation  NIMHANS 
Address  Department of Neurosurgery National Institute of Mental Health and Neurosciences (NIMHANS) Bengaluru

Bangalore
KARNATAKA
560029
India 
Phone  9898073843  
Fax    
Email  neurodhaval@rediffmail.com  
 
Source of Monetary or Material Support  
National Institute of Mental Health and Neurosciences (NIMHANS) 
 
Primary Sponsor  
Name  NIMHANS 
Address  Department of Neuromicrobiology NIMHANS, Banglore, 560029, Karnatka 
Type of Sponsor  Research institution 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Rosemary Shaji V  National Institute of Mental Health and Neurosciences (NIMHANS)  Department of Neuromicrobiology 1st floor of Administrative building
Bangalore
KARNATAKA 
7025087746

rosemaryshajiv@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Departmental Ethical Sub-comitte (DESC)  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Healthy Human Volunteers  Healthy, age- and sex-matched individuals without major illnesses or recent use of Antibiotics or probiotics, consenting to participate. 
Patients  (1) ICD-10 Condition: G968||Other specified disorders of central nervous system,  
 
Intervention / Comparator Agent  
Type  Name  Details 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  80.00 Year(s)
Gender  Both 
Details  1)Patients diagnosed with aneurysmal subarachnoid hemorrhage (aSAH), confirmed by imaging
2)Admission to the ICU/ ward within 72 hours of symptom onset.
3)Consent to participate in the study.
 
 
ExclusionCriteria 
Details  1) Pre-existing neurological or gastrointestinal disorders
2) Recent use of antibiotics or probiotics within 4 weeks prior to admission.
3) Non-aneurysmal subarachnoid hemorrhage
4) Mycotic aneurysms or aneurysms within arteriovenous malformations.
5) Pregnancy
 
 
Method of Generating Random Sequence   Not Applicable 
Method of Concealment   Not Applicable 
Blinding/Masking   Not Applicable 
Primary Outcome  
Outcome  TimePoints 
Identification and comparison of gut microbiome composition, short-chain fatty acid (SCFA) levels, and gut integrity biomarkers (zonulin, occludin, claudin-5) between aneurysmal subarachnoid hemorrhage (aSAH) patients and healthy controls, and their association with the development of cerebral vasospasm (CV) and delayed cerebral ischemia (DCI).  All biological samples (blood and stool) will be collected within 72 hours of diagnosis in aSAH patients, and once at enrollment in healthy controls. Clinical outcomes (CV and DCI) will be monitored daily for 14 days or until discharge. 
 
Secondary Outcome  
Outcome  TimePoints 
1) Correlation between specific gut microbiome signatures and the occurrence/severity of cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) in aSAH patients.

2)Association of altered short-chain fatty acid (SCFA) levels (acetate, propionate, and butyrate) with clinical outcomes in aSAH, including CV and DCI.

3)Correlation between blood levels of gut barrier integrity biomarkers (zonulin, occludin, claudin-5) and radiological or clinical evidence of cerebral vasospasm and delayed cerebral ischemia.

4)Comparison of gut microbiome diversity (alpha and beta diversity) between aSAH patients and healthy controls.

5)Exploratory identification of potential microbial or biomarker-based predictive tools for clinical outcomes in aSAH. 
All biological samples (blood and stool) will be collected within 72 hours of diagnosis in aSAH patients, and once at enrollment in healthy controls. Clinical outcomes (CV and DCI) will be monitored daily for 14 days or until discharge. 
 
Target Sample Size   Total Sample Size="90"
Sample Size from India="90" 
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   N/A 
Date of First Enrollment (India)   03/10/2025 
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="3"
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
  1. What data in particular will be shared?
    Response - Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).

  2. What additional supporting information will be shared?
    Response -  Statistical Analysis Plan

  3. Who will be able to view these files?
    Response - Researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.

  4. For what types of analyses will this data be available?
    Response - To achieve aims in the approved proposal.

  5. By what mechanism will data be made available?
    Response - Proposals should be directed to [rosemaryshajiv@gmail.com].

  6. For how long will this data be available start date provided 03-10-2025 and end date provided 03-10-2028?
    Response - Immediately following publication. No end date.

  7. Any URL or additional information regarding plan/policy for sharing IPD? 
    Additional Information - NIL
Brief Summary  

This research proposal outlines a prospective, observational cohort study investigating the role of the gut-brain axis in Aneurysmal Subarachnoid Hemorrhage (aSAH), a life-threatening condition associated with high morbidity and mortality. The study aims to address a critical gap in neurocritical care by exploring how the gut microbiome and its metabolic byproducts influence the disease progression and its further complications, specifically cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). This study adopts an integrated omics approach, combining genomics and metabolomics to provide a holistic view of this complex interaction. A total of 90 participants, 45 aSAH patients and 45 healthy controls will be enrolled, with samples collected within 72 hours of hospital admission. The research methodology includes several key steps such as 16S rRNA gene sequencing will be performed on stool samples to comprehensively profile the gut microbiome signature and identify specific gut bacterial biomarker Simultaneously, plasma levels of short-chain fatty acids (SCFAs), which are vital metabolites known to modulate inflammation and maintain gut barrier integrity, will be quantified using Gas Chromatography-Mass Spectrometry (GC-MS). Furthermore, the study will measure blood levels of key tight-junction proteins, namely Zonulin, Occludin, and Claudin-5, using ELISA to assess the integrity and permeability of the intestinal and blood brain barriers. By establishing a link between gut dysbiosis, altered metabolite profiles, and barrier dysfunction with aSAH outcomes, this research seeks to identify novel biomarkers and create the potential for new diagnostic tools and personalized therapeutic strategies. This groundbreaking study is the first of its kind to be conducted in the Indian population, offering a unique opportunity to understand these mechanisms in a diverse and understudied cohort.







































 
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