The iHealth-T2D study: rationale and design of a cluster randomised trial for prevention of Type 2 Diabetes amongst South Asians with central obesity and prediabetes

Background People from South Asia are at increased risk of type 2 diabetes (T2D). There is an urgent need to develop approaches for prevention of T2D in South Asians, that are cost-effective, generalisable and scalable across settings. Hypothesis Compared to usual care, risk of T2D can be reduced amongst South Asians with central obesity or raised HbA1c, through a 12 month lifestyle modification programme delivered by community health workers. Design Cluster randomised clinical trial (1:1 allocation to Intervention or Usual care), carried out in India, Pakistan, Sri Lanka, and UK, with 30 sites per country (120 sites total). Target recruitment 3,600 (30 participants per site) with annual follow-up for three years. Entry criteria South Asian, men or women, age 40-70 years with i. Central obesity (waist circumference ≥100cm in India and Pakistan; ≥90cm in Sri Lanka) and / or ii. Prediabetes (HbA1c 6.0-6.4% inclusive). Exclusion criteria: known type 1 or 2 diabetes, normal or underweight (body mass index<22kg/m2); pregnant or planning pregnancy; unstable residence or planning to leave the area; serious illness. Endpoints The primary end point is new onset T2D at 3 years, defined as: i. HbA1c≥6.5% or ii. Physician diagnosis and on treatment for T2D. Secondary endpoints at 1 and 3 years are: i. Physical measures: waist circumference, weight and blood pressure; ii. Lifestyle measures: smoking status, alcohol intake, physical activity, dietary intake; iii. Biochemical measures: Fasting glucose, insulin and lipids (total and HDL cholesterol, triglycerides); and iv. Treatment compliance. Intervention Lifestyle intervention (60 sites) or Usual care (60 sites). Lifestyle intervention was delivered by a trained community health worker over 12 months (5 one-one session, 4 group sessions, 13 telephone sessions) with the goal of the participants achieving e a 7% reduction in body mass index and a 10 cm reduction in waist circumference through i. improved diet and ii. increased physical activity. Usual care comprised a single 30 minute session of lifestyle modification advice from the community health worker. Results We screened 33,212 people for inclusion into the study. We identified 10,930 people who met study entry criteria, amongst whom, 3,682 agreed to take part in the intervention. Study participants are 49.2% female and aged 52.8 (SD 8.2) years. Clinical characteristics are well balanced between Intervention and Usual care sites. More than 90% of follow-up visits are scheduled to be complete December 2020. Based on follow-up to end 2019, the observed incidence of T2D in the study population is in line with expectations (6.1% per annum). Conclusion The iHealth-T2D study will advance understanding of strategies for prevention of diabetes amongst South Asians, use approaches for screening and intervention that are adapted for low-resource settings. Our study will thus inform the implementation of strategies for improving the health and well-being of this major global ethnic group. IRB approval 16/WM/0171 Trial registration EudraCT 2016-001350-18. Registered 14 April 2016 ; ClinicalTrials.gov [NCT02949739][1]. Registered 31 October 2016, , First posted 31/10/2016. Funder European Commission (award 643774) and National Institute for Health Research (award 16/136/68) ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial EudraCT 2016-001350-18. Registered 14 April 2016 https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/ihealth-t2d/ ; ClinicalTrials.gov [NCT02949739][1]. Registered 31 October 2016, https://clinicaltrials.gov/ct2/show/[NCT02949739][1], First posted 31/10/2016. ### Funding Statement The research was supported by the European Union H2020 program (iHealth-T2D, 643774). JCC, JSK, GF BR and WS are also supported in part by the National Institute for Health Research (NIHR) (16/136/68) using UK aid from the UK Government to support global health research. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR or the UK Department of Health and Social Care. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics approval and consent to participate Ethical approval was obtained from the Institutional Review Board in each participating country and at each research location before the start of the study. Information sheets and consent forms were made available in the major South Asian languages. Multilingual translators were available as required. Each participant provided informed consent. People unwilling or unable to provide consent were excluded from the study. India Max Healthcare Institutional Ethic Committee (ref: CT/MSSH/SKT-2/ENDO/IEC/14-40, date 22/04/16) Indian Council for Medical Research (ICMR, ref: 55/7/Indo-Foreign-Diab/2014-NCD-II, date 08/02/2016) Pakistan Punjab Institute of Cardiology Ethical Committee (ref: rtpgme-research-047, date 09/04/16) Services Institute of Medical Sciences Institutional Review Board (ref: IRB/2016/222/SIMS, date 12/03/16) Sri Lanka University of Colombo Ethics Review Committee (ref: EC-16-063, date 23/05/16) University of Kelaniya Ethics Review Committee (ref: P/62/05/2016, date 11/05/16) UK West Midlands - Solihull Research Ethics Committee (ref: 16/WM/0171, date 14/04/2016) All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data will be available to others on completion of the research, by application to the Steering Committee. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02949739&atom=%2Fmedrxiv%2Fearly%2F2020%2F11%2F13%2F2020.11.12.20230433.atom