Study protocol for a cluster randomized controlled trial for 16 weeks to assess the effect of almond consumption on glycemic control and gut health in prediabetes adults in rural settings of India

IntroductionAlmonds have prebiotic potential to maintain gut health and regulate glycemia. Western studies have shown their positive effects in preventing non-communicable diseases like diabetes and CVDs. However, there is a lack of well-designed studies involving Asian Indians, who have a higher predisposition to diabetes due to their unique Asian phenotype. Therefore, this study aims to evaluate the impact of almond supplementation on glycemic control and gut health in prediabetic adults in rural India through a randomized clinical trial. Methods and AnalysisA parallel cluster randomized controlled trial with 178 prediabetic participants aged 20-50, both genders, with a BMI of 18.9-25 kg/m2, will be conducted in rural areas of Chikkaballapur, Kolar, and rural Bangalore districts in India. The intervention group will receive 56g of almonds as mid-morning snacks for 16 weeks, while the control group will receive cereal pulse based traditional isocaloric snacks under the closed supervision of the study investigators. Anthropometry, clinical, and biochemical parameters will be measured at 0, 8th, and 16th weeks, and a subgroup of 120 participants will undergo gut health analysis. GLP 1 analysis will be conducted on 30 participants at 0 and 16th week. Statistical analysis will be performed using SPSS for Windows V 27.0, and both ITT and per-protocol analyses will be conducted. Ethics and DisseminationEthics approval was obtained from the Institutional Ethics Committee at Ramaiah Medical College, Bangalore, Karnataka, India (DRPEFP7672021). Results from this trial will be disseminated through publication in peer-reviewed journals, national and international presentations. Trial Registration NumberThe trial is registered in the clinical trial registry of India (CTRI/2023/03/050421). ARTICLE SUMMARYStrengths and Limitations: - The study is the first field-based trial in rural settings to assess the effect of almond consumption versus traditional cereal pulse-based snacks on prediabetes adults glycemic control and gut health. - The compliance management is crucially designed by performing an intervention on one-to-one closed supervision, assessment of serum tocopherol levels, and regular follow up of any adverse events. - The upcoming metagenomic analysis and the gut metabolites like short chain fatty acids (SCFA) and GLP 1 will significantly advance our understanding of the impact of almonds on the gut health of prediabetes adults. - A potential limitation of the study is that it will not be feasible to follow the participants after the post intervention period.