| CTRI Number |
CTRI/2025/03/082087 [Registered on: 10/03/2025] Trial Registered Prospectively |
| Last Modified On: |
25/02/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Other (Specify) [Prebiotic (Resistant Starch or High Amylose Maize Starch)] |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
How the gut and brain interact to affect cognitive and behavioral aspects of alcoholism |
|
Scientific Title of Study
|
Exploring the association of gut-brain axis with cognitive and behavioural aspects of alcohol use disorder |
| 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 Shree Mishra |
| Designation |
Assistant Pofessor |
| Affiliation |
ALL INDIA INSTITUTE OF MEDICAL SCIENCES, BHUBANESWAR |
| Address |
Room no 16, Department of Psychiatry, All India Institute of Medical Sciences, Sijua, Patrapada, Bhuabneswar
Khordha
ORISSA
751019
India |
| Phone |
8249255952 |
| Fax |
|
| Email |
psych_shree@aiimsbhubaneswar.edu.in |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Shree Mishra |
| Designation |
Assistant Pofessor |
| Affiliation |
ALL INDIA INSTITUTE OF MEDICAL SCIENCES, BHUBANESWAR |
| Address |
Room no 16, Department of Psychiatry, All India Institute of Medical Sciences, Sijua, Patrapada, Bhuabneswar
ORISSA
751019
India |
| Phone |
8249255952 |
| Fax |
|
| Email |
psych_shree@aiimsbhubaneswar.edu.in |
|
Details of Contact Person
Public Query
|
| Name |
Dr Shree Mishra |
| Designation |
Assistant Pofessor |
| Affiliation |
ALL INDIA INSTITUTE OF MEDICAL SCIENCES, BHUBANESWAR |
| Address |
Room no 16, Department of Psychiatry, All India Institute of Medical Sciences, Sijua, Patrapada, Bhuabneswar
ORISSA
751019
India |
| Phone |
8249255952 |
| Fax |
|
| Email |
psych_shree@aiimsbhubaneswar.edu.in |
|
|
Source of Monetary or Material Support
|
| Department of Science and Technology, Cognitive Science Research Initiative, KIRAN, Ministry of Science and Technology, Government of India |
|
|
Primary Sponsor
|
| Name |
Dr Shree Mishra |
| Address |
Room no 16, Department of Psychiatry, All India Institute of Medical Sciences, Sijua, Patrapada, Bhubaneswar, 751019, Odisha, India |
| Type of Sponsor |
Other [SELF] |
|
|
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 Shree Mishra |
ALL INDIA INSTITUTE OF MEDICAL SCIENCES, BHUBANESWAR |
Room no 16, Department of Psychiatry, All India Institute of Medical Sciences, Sijua, Patrapada, Bhubaneswar
Khordha
ORISSA |
8249255952
psych_shree@aiimsbhubaneswar.edu.in |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, BHUBANESWAR |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: F102||Alcohol dependence, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
High Amylose Maize Starch or HAMS |
95 grams daily for 6 weeks |
| Comparator Agent |
Treatment as Usual |
Dietary intake as usual |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
50.00 Year(s) |
| Gender |
Male |
| Details |
Patient meeting criteria for Alcohol Dependence according to ICD 10 criteria.
Patient with SADQ or Severity of Alcohol Dependence Questionnaire score greater than 16. |
|
| ExclusionCriteria |
| Details |
Patients body mass index or BMI greater than 30 kg per m2
Patients with diabetes
Patients with chronic inflammatory disease such as rheumatoid arthritis, inflammatory bowel disease
Patients with cancer
Patients who took antibiotics, glucocorticoids, or nonsteroidal anti-inflammatory drug for 2 months preceding the enrolment
Patient having overt liver disease, cirrhosis |
|
|
Method of Generating Random Sequence
|
Adaptive randomization, such as minimization |
|
Method of Concealment
|
Case Record Numbers |
|
Blinding/Masking
|
Participant Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
Cognitive Assessment according to Cambridge Neuropsychological Test Automated Battery or CANTAB
Stool sample assessment for , short chain fatty acid, absolute and Relative abundance of bacterial species |
-3 day, 0 day, 30 days, 60 days, 90 days, 180 days |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Clinical Institute Withdrawal Assessment Alcohol -revised (CIWA-ar) score
Obsessive Compulsive Drinking Scale (OCDS) score
Barratt Impulsiveness Scale score
Readiness to Change Questionnaire (RCQ) score
Severity of Alcohol Dependence Questionnaire (SADQ) score
Social Cognition Rating Tools in Indian Setting (SOCRATIS) score
p300 Event related potential (ERP)
|
-3 day, 0 day, 30 days, 60 days, 90 days, 180 days |
|
|
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)
|
02/05/2025 |
| 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 - NO
|
|
Brief Summary
|
There has been an emerging interest in understanding the neurobiological and
behavioural components of alcohol addiction pertaining the role of gut brain axis.
Motivation, salience, craving for the addictive substance and the negative emotional
state ridden relapses are important behavioural aspects in continuing the addiction
trajectory. Although a number of molecules as anti -craving agents have been tried in
alcohol dependence; they largely target the neurochemical milieu of reward pathway
in brain. However, the response to these molecules is not uniform, neither long lasting.
Hence exploring the missing link of gut brain axis in pro addictive cognitions and
behaviour is important.
Addictive disorders esp. alcohol dependence is linked with neuropsychological deficits
viz. visuospatial processing, attention, memory, executive functioning esp. impaired
set shifting, response inhibition, poor decision making, planning and organising. known
to perpetuate the cycle of addiction and relapses. In various preclinical and few human
studies, chronic alcohol consumption has been shown to cause alteration in the gut
microbial flora and changes in the gut luminal barrier. The resident bacterial products
especially endotoxins (especially lipopolysaccharide), of certain specific gut bacteria
might have a role in triggering brain inflammatory processes either via hepatic
circulation or through the vague nerve. This in turn can modulate various cognitive,
emotional and behavioural aspects of addictive disorders.
Restoring the altered gut microbiome constitution via (pre/probiotic) towards a healthy
state might remodulate the gut brain dysbiosis and resulting neuron-inflammation.
These agents are either This could indirectly impact the altered cognitive and
emotional processes in context of alcohol addiction. In this regard, introducing
Probiotics and prebiotics is one way of facilitating healthy gut microbiome. these are
either live bacterial stains or nondigestible carbohydrates which facilitate healthy
microbiome in the gut respectively. Prebiotics are essentially the non-digestible
carbohydrates; resistant to alpha amylase, facilitate healthy gut bacteria and produce
fermentation products viz. short-chain fatty acids (SCFAs), including acetate,
propionate, and butyrate. Butyrate has a role in cell proliferation via gene regulation
and epigenetic mechanism.
Interventions involving gut microbiome alteration using pre or probiotics has been
done in alcoholic and non-alcoholic liver conditions. However, studies exploring its role
in addictive behaviours are still in early stages. High Amylose maize Starch (HAMS)
meets the criteria for safety, durability, and availability as a dietary intervention for gut
inflammation in pre-existing clinical research. However, the role of prebiotics has not
been widely studied in its effect in altering behavioural aspects of alcohol addiction via
the similar gut microbiota altering processes. Hence our study will attempt to explore
the role of high amylose maize starch as a prebiotic agent in facilitating the healthy gut
microbiota and altering the behavioural aspects of addiction esp. craving and
motivation in subjects with alcohol use disorder along with the conventional antic
raving medications and psychological therapies.
The symptoms of alcohol tolerance and withdrawal, with uncontrolled intake and
craving, are the core symptoms of alcohol addiction, indicating neurologic adaptation
or so-called physiologic dependence. Personality traits esp. impulsivity (attentional,
motor, and non-planning impulsiveness) make susceptible individuals more prone to
seek substance associated positive emotional state. (Coskunpinar A, Dir AL, Cyders
MA. 2013.) Multidimensionality in impulsivity and alcohol use: a meta-analysis using the UPPS
model of impulsivity. The severity of alcohol addiction is correlated with the intensity
of their craving, cognitive dysfunction, anxiety, and depressive symptoms. As we
mentioned above, systemic inflammation may play an important role in the
development of alcohol addiction; gut barrier dysfunction and inflammation in both the
gut and liver may contribute to peripheral inflammation and cause brain inflammation
, inducing inflammation of brain cells such as microglia or astrocytes . The sickness
behaviour theory may link systemic inflammation to both alcohol addiction and mood
disorders .
This theory supports that peripheral inflammation, such as leaky gut, activates the
immune system and produces cytokines that can reach the brain, causing fever,
fatigue, lassitude, inability to concentrate, and withdrawal from social interactions;
when the above behaviours persist, depressive symptoms may develop . Though
studies support alcohol addiction or craving is associated with systemic inflammation,
the causality is still unclear. Nevertheless, the combination of alcohol craving and
negative emotions such as anxiety and depression are highly associated with drug-seeking behaviours and relapse, indicating that reducing systemic inflammation may
improve psychological well-being and prevent relapse. |