The SKAN-HASP Study embarks on a transformative decade-long journey, dedicated to exploring the intricate world of risk factors associated with ischemic stroke and heart attacks. The study goes beyond conventional research; it aspires to craft a dynamic and personalized risk calculator for individuals. This endeavour is novel in its essence, as it seamlessly unites the paradigms of Allopathic and Ayurvedic medicine while delving into the profound realm of the Gut-Brain Axis. The goal is not merely prediction; it is the prescription of preventative lifestyle modifications and the advocacy of gentle therapies that can reduce an individual's susceptibility to stroke and cardiovascular diseases (CVDs).
Burden of Ischemic Stroke and Heart Attack:
Ischemic stroke is a global health concern. It's the leading cause of disability and cognitive impairment. Ischemic strokes account for over 70% of all strokes and contribute substantially to worldwide all-cause mortality. The incidence of ischemic stroke in individuals under 70 has risen by 22% in recent years. In India, lower-income groups experience 3.6 times higher mortality and 3.7 times higher disability-adjusted life years from ischemic stroke.
Burden of Heart Attack:
Cardiovascular diseases (CVDs) stand as the world’s foremost cause of death, exacting a significant toll of around 17.9 million lives annually. Globally, CVDs were responsible for 31.8% of all deaths and 14.7% of Disability Adjusted Life Years (DALYs) in the year 2017. Over 80% of CVD cases and related deaths occur in low- and middle-income countries. Heart attack shares risk factors with ischemic stroke, with some differences. Additional assessments like Echocardiography and Doppler are considered. Dyslipidemia is strongly associated with heart attacks.
Ischemic stroke and heart attacks are significant causes of morbidity and mortality globally. Traditional risk factors have been studied, but emerging biomarkers show stronger predictive value. The role of healthy gut microbiome and its role in stroke and CVDs is being explored through the study.
The SKAN cohort includes individuals aged 30 to 80, monitored for over a decade. Allopathic and Ayurvedic medicine principles are combined for a comprehensive approach. Gut health status is assessed over time to enhance predictive power.
Two organizations, NH and TDU, are responsible for managing cohorts following Allopathic and Ayurvedic systems of medicine. Another SKAN-RT cohort promotes healthy lifestyle practices. The study aims to provide 3 independent predictive models which can be integrated into a comprehensive risk calculator.
The study is structured into three phases: Pilot, Implementation, and Translation. A specialized data collection instrument has been developed to ensure standardized and thorough data collection. Data is collected through questionnaires, tests, clinical examinations, and securely stored. The pilot study is planned for a period of 1 year (from 1st January 2024 to 1st January 2025.)
Sample size calculations have been performed for different distributions to accommodate cohort-based studies.
Inclusion and Exclusion Criteria
Inclusion criteria are age, stroke-free and CVDs-free status on the date of enrolment, with willingness to participate. Exclusion criteria include chronic debilitation and a history of stroke or heart disease.
The study involves statistical analyses such as descriptive statistics, frequency analysis, cross-tabulation, data visualization, and Pareto analysis to assess data quality.
In summary, the SKAN-HASP Study is a comprehensive research project aiming to understand and mitigate the risks of ischemic stroke and heart attacks in the Indian population, with a unique approach that combines traditional and Ayurvedic medicine principles and considers the Gut-Brain Axis. The study seeks to develop predictive models to help doctors to select appropriate therapies / medications and individuals to manage their health risks effectively.
The partner institutes for this project are Hirabai Cowasji Jehangir Medical Research Institute (HCJMRI), Pune & KMCH Research Foundation, Coimbatore. Type 1 diabetes mellitus (T1DM) is an auto-immune disorder that occurs in a genetically susceptible individual due to certain environmental triggers resulting in destruction of insulin secreting pancreatic cells. According to a recent report, India is ranked 59th in the world with an incidence of 4.2 T1DM cases per 100,000 populations (IDF, 2021).
Hundred and thirty-one children diagnosed with T1DM and 79 healthy children have been enrolled by HCJMRI as participants for the study. Data entry has been completed for all enrolled participants, while data compilation is in process. Additionally, blood and stool samples for a total of 210 children have been collected. 210 stool samples have been submitted to SKAN Research trust for microbiome analysis. Enrolment of 20 subjects with T1DM and 1 healthy control as subjects is yet to be done. Researchers from KMCH Research Foundation, Coimbatore have been provided training on data collection procedure and administration of cognition testing. More than 50% data collection has been achieved.
120 children with type 1 diabetes were pre identified and received oral consent from both the children and their parents by KMCH Research Foundation for participation in the study. The written informed consent will be obtained during enrolment and sample collection. The team travelled to Jehangir Medical Research Institute to receive training in performing the BKT test for cognitive testing. Further, it will be ensured that all procedures including data collection, blood anthropometry and sample collection are being performed in a coordinated manner. Samples collection has started after performing BKT test. Until now, 35 samples have been collected from children with T1DM condition. The process of identifying the age and sex matched healthy controls for this study is underway. Data and sample collection has been completed for 35 children diagnosed with T1DM.
The partner institute for this project is National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru. This project aims to assess any changes in the microbiome starting from the hospital admission till acute antipsychotic therapy administered as part of standard medical procedure.
The project is currently in the second month and progressing. Advertisement and Recruitment of staff nurse for the project has been done. NIMHANS has finalized the questionnaire for the alcohol and tobacco use in the study with the guidance of Dr. Jayant Mahadevan, Centre for Addiction medicine, NIMHANS. Technical training has been provided to Ms. Harshitha (the nurse recruited for the project work) about using various assessment tools like brief psychiatric rating scale etc. Clinical assessment of at least 15 patients included in the pilot study was conducted by Ms. Harshitha and was discussed with the team on regular basis. The inputs received from the team were implemented to improve the clinical assessment. NIMHANS has started patient recruitment process since the past 3 weeks, looking for cases which match the inclusion criteria in the psychiatry wards, with the help of senior residents and ward staff on daily basis. Around 55 admitted patients were assessed - none of them met the criteria set by NIMHANS, which implies either the patients were under antipsychotic medications / antibiotics, or were elderly, or having gastro-intestinal illnesses or thyroid dysfunctions. Also, NIMHANS found difficulty in recruiting the patients as most individuals are on psychotropic medications (patients on antidepressants/ mood stabilisers).
St John’s Medical College & Hospital/ St John’s Research Institute/ St John’s Geriatric Centre.
The "SOHAM Cohort Study" emerges against the backdrop of the global imperative of Healthy Ageing, a concern shared by India, where the absence of precise tools to identify "healthy ageing" individuals impedes the understanding of factors contributing to chronic diseases in this demographic. With India's elderly population projected to grow significantly, reaching 12% by 2025 and nearly 20% by 2050, the need for a comprehensive, locally adapted tool covering all domains and biomarkers to identify "Healthy Ageing" is paramount. This initiative aims to address this gap and contribute to the development of effective prevention strategies, ultimately reducing avoidable ill health in the ageing population. Over the past year, significant progress has been made in the project. The conceptualization and planning of the study, including defining its scope, objectives, and methodology, have been completed. The design of the "SOHAM Study" has been finalized, comprising two parts: the drafting, enriching, refining and validating of the Healthy Aging Tool - India (HAT-I) in Part 1, and the longitudinal follow-up of a large number of subjects assessed with the HAT-I tool for aging trajectory analysis in Part 2. Ethical clearance for the research project has been obtained, and a diverse team of professionals have been assembled through staff recruitment. The team has undergone intensive training to ensure data accuracy and competence. The project has achieved several milestones, including the completion of drafting, enrichment, and refinement components of the study. The qualitative study has been submitted as a manuscript, and the recruitment process for the validation study has been initiated.
Centre for Brain Research (CBR), Indian Institute of Science and National Institute of Mental Health and Neurosciences.
The study aims to provide a better understanding of the complex interplay of genetic, molecular, and environmental interactions as causation factors for both young and late onset Parkinson’s Disease (PD). Results from this study will not only help in examining the different causation factors for both forms of PD but also aid in developing improved prognostic measures against the disease. To achieve the study objectives, longitudinal follow up of PD patients, with detailed neurological and neuropsychological evaluation will be undertaken. In parallel, studies on mouse models will aid in understanding the molecular underpinnings of motor and non-motor symptoms of PD. So far, 180 samples from the total target of 1000 have been collected and processed for DNA extraction. Genome Wide Association Study (GWAS) analysis has been completed for 98 of these samples and another 96 samples are currently being processed for NGS and GWAS. A key achievement of the study thus far has been the successful establishment of a slow progressing mouse model of PD.
The clinical components of the YLOPD study are managed by NIMHANS. The broad objectives of this cohort are to gather data on clinical and genetic. neuroimaging and neurophysiological characterization of a large Indian young onset PD (YOPD, age at onset ≤45 years) and late onset PD (LOPD; age at onset greater than 45 years) and to identify probable biomarkers for early detection, monitoring progression (over 5 years), prognostication of disease and response to different medical and surgical therapeutic strategies.
The partner institute for this project is the National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru and Narayan Hospitals (NH).
This is a large cohort study aimed at understanding the natural history of stroke employing a mixed cohort study design (Retrospective-Prospective cohort study). This will be conducted in Mulbagal taluka of Kolara district and select urban wards of Bengaluru city. Sampling strategy has been finalized. The estimated sample size of 2 lakh people aged 30 years and above will be followed up for a period of 4 years as ‘stroke-free cohort’, stratified based on a set of risk factors such as obesity, stress, substance use, and diet/physical activity, other NCDs cohorts amongst the eligible population of ~4 lakh. After the first-ever incidence of stroke among participants, a new cohort named ‘stroke cohort’ will be formed utilizing a prospective cohort study design consisting of an expected case load of ~750 cases over 3 years. The study also adopts the Quasi Experimental Pre-Post intervention study design to a sample of 255 stroke cases to study the effectiveness of a Comprehensive Acute Stroke CAre moDEl (CASCADE model) developed to improve preparedness, management of stroke, ensuring improved survival, reduced disability, and enhanced quality of life of stroke patients. Monitoring protocol and format has been developed through workshop. Clinical Trial Registry India (CTRI) registration number has been obtained for this study. Specific achievements are Stroke-free, Stroke and Hospital preparedness questionnaire near final, protocols finalized and approved by the Expert advisory group. The approvals of IEC for all the amendments in the protocol were obtained.
S-VYASA, TDU & SOUKYA
The occurrence of diabetes mellitus (DM) is steadily on the rise and has rapidly emerged as one of the most widespread and costly chronic illnesses worldwide. There is a strong and direct connection between DM and cardiovascular disease (CVD), which stands as the most prevalent cause of illness and premature death among individuals with diabetes. Common cardiovascular (CV) risk factors like obesity, hypertension, and dyslipidemia are frequently observed in DM patients, significantly elevating their susceptibility to heart-related issues. Managing and preventing cardiovascular diseases in individuals with diabetes is a critical aspect of diabetes care. Effective management includes working closely with healthcare providers, following a personalized care plan, and adopting a heart-healthy lifestyle. Yoga is a valuable component of a heart-healthy lifestyle and offers numerous physical and mental health benefits. It complements other aspects of heart health, such as maintaining a nutritious diet, regular exercise, and stress management, which can help manage diabetes in turn resulting in overall well-being.
To test the effectiveness of long-term yoga-based lifestyle intervention (YBLI) on common cardiovascular health and remission of type 2 diabetes.
The study is divided into two parts; investigating effectiveness of different yoga modules on cardiovascular dysfunction and diabetes independently.
Yoga intervention on cardiovascular health: This study includes two-phases:
Yoga intervention related to type 2 diabetes remission: This study is implemented in 2 phases. Phase 1- to compare 30 min yoga module with standardised 60 min module for its efficacy in managing hyperglycaemia and Phase-2, a longitudinal single arm study to assess adherence of participants to specified intervention and possible remission of type-2 diabetes.
Work done during the last one year.
Biochemical Panel standardization for 20 analytes at Randox Monaco machine. Training staff on molecular biology techniques such as DNA extraction. Recruitment, blood sample collection and storage for n=60 subjects. Conceptualization and development of ‘Yoga lifestyle for Diabetes’ booklet to be provided to the study participants.
Indian Institute of Technology Roorkee and NIMHANS
A major lack of understanding about the pathophysiology of bipolar disorder (BD) poses the greatest challenge in the development of highly efficacious treatments against this disease. Furthermore, symptoms of BD have considerable overlap with other neuropsychiatric diseases (like anxiety, depression, mania etc.) complicating existing symptom-based diagnosis. Although miRNA, proteomic and metabolic profiling of BD patients has been undertaken as diagnostic tools for BD, the role of exosomes has not been explored in a similar vein. This project aims to assess whether biochemical changes in exosomes of patients with BD and other allied neurological disorders (like anxiety, depression, mania etc.) can induce neurotoxicity in neuronal cell cultures. Further, based on the aforementioned situation of limited therapeutic options, a safer alternative to fight these neurological disorders is envisioned as a part of the study. To achieve the same, exploring nutraceuticals/dietary supplements has been targeted in this study, as these agents can act on multiple targets simultaneously. Studies on neuronal cell lines treated with reserpine and glutamine were conducted, and these identified different biomarkers expressed during cellular stress. Thus, an in-vitro neuronal cell-based BD model was developed, that is currently being validated for wider applicability. Data thus far reveal that co-treatment with these drugs leads to BD like symptoms in neuronal cell lines. Further, an in-vitro screening model for testing the potential of certain nutraceuticals such as honey and an ayurvedic polyherbal formulation for the prevention/ management of BD has been developed. Currently the study is in progress to understand its underlying mechanism of action. Another achievement of the project has been the revelation that serum constitutes of BD patients impact the normal functioning of neuronal cell cultures in-vitro.
Narayana Health and NIMHANS
Stroke causes neuro-restoration that remains variable and treatment of stroke-caused infarct and penumbra is challenging. Standard stroke care includes thrombolysis, mechanical thrombectomy, decompressive craniectomy if indicated, and early rehabilitation. In addition to above treatments, novel therapeutic modalities include stem cell therapy, neuromodulation, brain-machine interface, robotic rehabilitation and multimodal treatments. Stem Cell-Based Stroke Management Program includes collaboration between Mazumdar Shaw Medical Foundation (MSMF) and Narayana Institute of Neurosciences, MSMC under Narayana Health (NH), a program for the clinical application of stem cell treatment in stroke survivors.
To establish, identify markers of plasticity/recovery and modify stem cell treatment protocols to enhance functional recovery with augmentative techniques and assess the effects of these adjuncts on overall patient outcomes.
In last year, Advanced Stroke Monitoring Lab with Functional Transcranial Doppler, Transcranial Magnetic Stimulation (TMS), Functional EEG, Quantitative Motion Analysis, Computerized Cognitive Assessment to be used as an advanced stroke diagnostics facility. TMS and Transcranial Doppler device testing on healthy controls has been initiated. BSL2 Facility has been expanded and functional. cGMP facility has been initiated and is in progress in consultation with a regulatory expert with Standard operating protocols being developed. The project has been divided into 5 phases for stroke, phases 1A to 1C will focus on discerning the effects of hyperbaric oxygen (HBOT), augmented reality, and robotic rehabilitation in different phases of stroke recovery. Phase 2A and 2B will focus on the effects of stem cells and adjuncts on recovery from stroke. The in vitro studies to see effect of HBOT on viability, proliferation, and molecular profile in human astrocytes (HA), glioma cells (U251) are being assessed along with Bone-marrow derived mesenchymal stem cell line (Hs_5) in future. Project milestones achieved are IEC Approval and patient recruitment for the HBOT and robotic rehabilitation trials. Manuscripts under preparation; use of adjunctive hyperbaric oxygen and peripheral magnetic stimulation (device procured from SKAN grant), and functional transcranial Doppler in healthy controls.
The Quadram Institute Bioscience (QIB) and SKAN Research Trust have forged a Comprehensive Partnership Agreement on May 19, 2023, to jointly address gut health and pioneer gut-based therapies for combating ageing and neurological diseases. QIB, a prominent UK national science entity, is dedicated to advancing healthier lives through innovations in gut health, microbiology, and food sciences. The collaboration outlines various key areas of cooperation, including joint research projects in the UK and India to develop microbiome-based products for human health, technology transfer from QIB to SKAN, training of SKAN research scientists at QIB, and the study of large Indian population cohorts to formulate therapies tailored to India's unique health challenges (ageing and neurological diseases). A specific research project, “Development of Phage Therapies to Alleviate Symptoms of Parkinson’s Disease”, has been identified under this collaboration. Dr Arjan Narbad from QIB and Dr Yogesh Shouche from SKAN will serve as principal investigators for this endeavour. The project aims to investigate the role of sulphate reducing bacteria (SRB) in the development of Parkinson's Disease (PD) and explore phage therapy as a targeted strategy for controlling SRB in the gut to potentially alleviate PD symptoms. Furthermore, three SKAN research scientists will undergo a year-long training program at QIB, supervised by Dr Arjan Narbad. SKAN will cover the training fees and consumables cost amounting to GBP 20,000 annually for each scientist. The training is expected to commence by the end of 2023. The overarching objectives of the research project involve conducting a comparative microbiome analysis of PD patients and healthy individuals, isolating and characterizing SRB and SRB-specific bacteriophages, and exploring the biocontrol of SRBs using phage therapy. The collaboration between QIB and SKAN holds promise for advancing scientific understanding and potential therapeutic interventions in the critical field of gut health and neurological diseases.
SKAN Research Trust (SKAN), and the UK-based Wellcome-MRC Cambridge Stem Cell Institute (CSCI), executed a series of partnership agreements on 6 September 2023 in Cambridge to further accelerate stem cell studies in SKAN and India. The agreements executed include the following:
SKAN – CSCI Consultancy Agreements-SKAN will upgrade its stem cell and bioinformatics facilities through inputs from CSCI and receive active assistance from CSCI to set up the SKAN Stem Cell Centre of Excellence.
SKAN – CSCI Joint Study- Dr Jyoti Nangalia, Group Leader at the Wellcome-MRC Stem Cell Institute and Wellcome Sanger Institute, will be the Principal Investigator of the first SKAN – CSCI joint study on “The genomic landscape of neurodegenerative diseases of ageing in an Indian cohort”. The joint project will be carried out on Indian cohorts, which will also create opportunities. During this period, SKAN researchers will be trained in top-of-the-line technologies at CSCI.
Cells in the human body accumulates somatic mutations with age and are also affected by intrinsic and extrinsic factors. Once acquired, these mutations are passed from parent cells to daughter cells in dividing tissues, accumulated at the latter parts of life. Many of these mutations result in a single cell dividing into an uncontrollable clonal expansion leading to cancer. Moreover, recent data suggest that somatic mutations also drive a multitude of non-cancerous diseases. These clones result in loss of resilience and susceptibility to disease upon ageing. How these clones trigger different disease, and to what extent their growth is modified by factors such as environmental exposures and genetic background/ethnicity, we can begin to understand how to modulate these clones to reduce susceptibility to disease. The joint project aims to characterise the role of these somatic mutations and clonal expansions in Indian patients suffering from neurodegenerative disorders of ageing.