AIM-WEIGHT is a clinical study evaluating whether a fixed microbiome-targeted nutritional supplement can support weight loss in adults with overweight or obesity who do not have prediabetes or diabetes. The formulation was developed using an artificial-intelligence-guided analysis of gut microbiome and metabolic-health data. The AI system will not select or modify treatment for individual participants during the study. Eighty participants will be randomly assigned to receive either the active nutritional supplement or a matching placebo for 24 weeks. Both groups will receive the same standardized lifestyle counselling. The main question is whether participants receiving the active supplement will have a greater percentage reduction in body weight after 12 weeks than those receiving placebo. The investigators hypothesize that the active intervention will produce greater weight loss. Assessments through Week 24 will also examine whether the effect is maintained during continued treatment, together with changes in waist circumference, general health measures, safety, treatment adherence, and gut microbiome features.
AIM-WEIGHT is a randomized, masked, placebo-controlled, parallel-group proof-of-concept study designed to obtain an initial controlled estimate of the efficacy and safety of a fixed microbiome-targeted nutritional intervention for weight management. The study is intended to determine whether the observed treatment signal is sufficiently promising to support a larger confirmatory trial and to provide a more precise estimate of the treatment effect for future study planning. The investigational formulation was selected before participant enrollment using an artificial-intelligence-guided formulation-development process. The AI methodology was used to inform the selection and dosing of candidate microbiome-active ingredients based on prior analyses of relationships between the gut microbiome and metabolic health. The resulting formulation is fixed and identical for all participants assigned to the active group. AI will not be used during the study for participant-level personalization, treatment assignment, dose modification, prediction, or clinical decision-making. Consequently, the study evaluates the clinical performance of the fixed formulation and is not designed as an independent validation of the AI algorithm. The study includes a 12-week primary weight-loss period followed by continued assigned intervention through Week 24. The Week 24 assessments are intended to provide supportive evidence regarding maintenance of the Week 12 effect during continued treatment. They should not be interpreted as evaluating maintenance after treatment withdrawal. The sample size is based on the primary endpoint of percentage change in body weight from baseline to Week 12. Assuming a between-group difference of 3.5 percentage points, a common standard deviation of 5.0 percentage points, and a two-sided significance level of 0.05, 34 evaluable participants per group provide approximately 81% statistical power. Allowing for approximately 15% attrition by Week 12, 80 participants will be randomized in total, with 40 assigned to each group. The primary analysis will compare randomized groups using analysis of covariance adjusted for baseline body weight and the prespecified randomization stratification factors.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE
Enrollment
80
A fixed, two-phase oral nutritional supplementation regimen developed using an AI-guided analysis of prior gut microbiome and metabolic-health data. All participants assigned to the active arm will follow the same prespecified regimen. During Weeks 0-12, participants will take two sachets and two capsules daily. During the maintenance supplementation period, Weeks 13-24, participants will take two capsules daily. The AI-guided process was used only during formulation development and will not personalize or modify the supplementation regimen for individual participants during the study.
A placebo formulated to match the active supplement in appearance, taste, smell, packaging, dosage form, administration schedule, and storage conditions. Participants will receive the placebo orally for two consecutive 12-week periods, for a total of 24 weeks. The placebo will not contain active prebiotic, probiotic, synbiotic, postbiotic, or other bioactive components expected to influence body weight or gut microbiome outcomes. The placebo will be administered as during Weeks 0-12, participants will take two sachets and two capsules daily. During Weeks 13-24, participants will take two capsules daily.
Participants in both study arms will receive identical standardized lifestyle counselling delivered by trained personnel using a predefined counselling manual. Each contact will last approximately 15-20 minutes and will provide general evidence-based guidance on balanced nutrition, portion awareness, and physical activity. The counselling will not constitute an individualized intensive calorie-restriction or behavioral weight-loss program.
Başakşehir Çam and Sakura City Hospital
Istanbul, Turkey (Türkiye)
Percent Change in Body Weight From Baseline to Week 12
Percent change in body weight will be calculated as 100 x \[(Week 12 body weight - baseline body weight) / baseline body weight\]. Negative values indicate weight loss. Body weight will be measured in kilograms to the nearest 0.1 kg using a calibrated digital scale after an overnight fast of at least 8 hours, in light clothing, without shoes, after voiding, and at approximately the same time of day. Two measurements will be obtained. If they differ by no more than 0.3 kg, their mean will be used. If they differ by more than 0.3 kg, a third measurement will be obtained and the median of the three measurements will be used.
Time frame: Baseline to Week 12
Percent Change in Body Weight From Baseline to Week 24
Percent change in body weight will be calculated as 100 x \[(Week 24 body weight - baseline body weight) / baseline body weight\]. Negative values indicate weight loss. Body weight will be measured in kilograms using the same standardized fasting measurement procedure used for the primary outcome. This outcome represents the cumulative body-weight change during the complete 24-week assigned supplementation period.
Time frame: Baseline to Week 24
Proportion of Participants Achieving at Least 5% Body-Weight Loss at Week 12
The proportion of participants whose Week 12 body weight is at least 5% lower than their baseline body weight will be determined. Percentage body-weight loss will be calculated as 100 x \[(baseline body weight - Week 12 body weight) / baseline body weight\]. Each participant will be classified as achieving or not achieving the 5% threshold.
Time frame: Baseline to Week 12
Change in Waist Circumference From Baseline to Week 12
Change in waist circumference will be calculated as Week 12 waist circumference minus baseline waist circumference and reported in centimeters. Negative values indicate a reduction. Waist circumference will be measured using a non-stretch tape at the midpoint between the lowest rib and the iliac crest. Two measurements will be obtained. If they differ by no more than 1.0 cm, their mean will be used. If they differ by more than 1.0 cm, a third measurement will be obtained and the median of the three measurements will be used.
Time frame: Baseline to Week 12
Proportion of Participants Achieving at Least 5% Body-Weight Loss at Week 24
The proportion of participants whose Week 24 body weight is at least 5% lower than their baseline body weight will be determined. Percentage body-weight loss will be calculated as 100 x \[(baseline body weight - Week 24 body weight) / baseline body weight\]. Each participant will be classified as achieving or not achieving the 5% threshold.
Time frame: Baseline to Week 24
Change in Waist Circumference From Baseline to Week 24
Change in waist circumference will be calculated as Week 24 waist circumference minus baseline waist circumference and reported in centimeters. Negative values indicate a reduction. Waist circumference will be measured using the same standardized procedure used for the Week 12 waist-circumference outcome. This outcome represents cumulative change during the complete 24-week assigned supplementation period.
Time frame: Baseline to Week 24
Change in Gut Microbiome Shannon Diversity Index From Baseline to Week 12
Gut microbiome alpha diversity will be calculated from shotgun metagenomic species-level relative abundance profiles using the Shannon diversity index. Change will be calculated as the Week 12 Shannon index minus the baseline Shannon index. Positive values indicate increased within-sample microbial diversity, and negative values indicate decreased within-sample diversity. Increased diversity will not necessarily be interpreted as clinical improvement. Week 12 is the principal exploratory microbiome time point and reflects exposure to the initial supplementation regimen.
Time frame: Baseline to Week 12
Change in Gut Microbiome Community Composition From Baseline to Week 12
Overall gut microbiome community composition will be evaluated from shotgun metagenomic species-level abundance profiles using Bray-Curtis dissimilarity. Bray-Curtis values range from 0 to 1, with larger values indicating greater compositional dissimilarity; larger values do not indicate a better clinical outcome. Differences between randomized groups in community change from baseline to Week 12 will be evaluated using a prespecified longitudinal permutation-based multivariate analysis with permutations constrained by participant. Multivariate dispersion will also be assessed.
Time frame: Baseline to Week 12
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