Overweight (Without Type 2 Diabetes) With Weight-related Comorbidities, Overweight (BMI > 25)
Conditions
Keywords
Obesity, Overwieght, Weight loss, Supplement, Artificial intelligence, Microbiome
Brief summary
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.
Detailed description
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.
Interventions
DIETARY_SUPPLEMENTAI-Guided Microbiome-Targeted Nutritional Supplement
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.
DIETARY_SUPPLEMENTMatching Placebo (B)
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.
BEHAVIORALLifestyle counselling
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.
Sponsors
Varol TUNALI
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The active intervention and placebo will be matched in appearance, taste, smell, packaging, administration schedule, and storage conditions. Laboratory personnel performing biomarker and microbiome analyses and the statistician performing the prespecified primary analysis will also remain masked to treatment allocation until database lock. Emergency unmasking will be permitted only when knowledge of allocation is essential for participant management, and every unmasking event will be documented.
Intervention model description
Two-arm, parallel-group study. Participants will be randomized in a 1:1 ratio to receive either the fixed AI-guided microbiome-targeted nutritional intervention or matching placebo for 24 weeks. Both groups will receive identical standardized lifestyle counselling. Randomization will be stratified by sex and baseline BMI category (25.0-29.9 kg/m² versus 30.0-40.0 kg/m²).
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 65 years, inclusive. * Body mass index of 25.0 to 40.0 kg/m2 at screening. * No previous diagnosis of prediabetes or diabetes. * Glycated hemoglobin (HbA1c) below 5.7% at screening. * Fasting plasma glucose below 100 mg/dL at screening. * Stable body weight, defined as a self-reported absolute change of no more than 5% or 3 kg, whichever is smaller, during the 3 months before screening. * Willing and able to provide written informed consent. * Willing and able to comply with study visits, assigned supplement or placebo use, and the assessment schedule. * Willing to provide fasting venous blood and stool samples according to the study schedule. * Willing to receive standardized lifestyle counseling during the 24-week blinded intervention period. * No systemic antibiotic use within 8 weeks before randomization. * No probiotic, prebiotic, synbiotic, or postbiotic supplement use within 12 weeks before randomization. * If hypertension or dyslipidemia is present, antihypertensive or lipid-lowering treatment must have been initiated and the dose must have remained unchanged for at least 3 months before randomization, with no treatment change planned at the time of randomization.
Exclusion criteria
* Prediabetes or diabetes identified by medical history, HbA1c, or fasting plasma glucose. * Use of glucose-lowering medication, including metformin, a glucagon-like peptide-1 receptor agonist, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 co-agonist, a sodium-glucose cotransporter-2 inhibitor, a dipeptidyl peptidase-4 inhibitor, a sulfonylurea, insulin, or another antidiabetic agent. * Use of a glucagon-like peptide-1 receptor agonist or glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 co-agonist for any indication within 12 months before randomization. * Use of another anti-obesity medication, including orlistat, naltrexone/bupropion, or phentermine/topiramate, within 6 months before randomization. * Planned initiation during the 24-week study of a weight-loss medication, structured commercial weight-loss program, very-low-calorie diet, or bariatric procedure. * History of bariatric surgery. * History of gastrointestinal surgery other than appendectomy or uncomplicated cholecystectomy. * Active inflammatory bowel disease, celiac disease, microscopic colitis, chronic pancreatitis, malabsorption syndrome, or another chronic severe gastrointestinal disease likely to affect nutrient absorption or study adherence. * Acute gastroenteritis within 4 weeks before randomization. * Colonoscopy bowel preparation within 12 weeks before randomization. * Fecal microbiota transplantation within 12 months before randomization. * Active malignancy or malignancy treated within 6 months before screening, except adequately treated non-melanoma skin cancer. * Stage 3b to 5 chronic kidney disease, defined as an estimated glomerular filtration rate below 45 mL/min/1.73 m2. * Decompensated liver disease or Child-Pugh class B or C liver disease. * Alanine aminotransferase or aspartate aminotransferase greater than 3 times the upper limit of normal at screening, unless judged clinically insignificant and approved by the investigator. * Untreated overt thyroid disease, or initiation or dose modification of thyroid medication within 3 months before randomization. Stable treated hypothyroidism is permitted. * Use of systemic corticosteroids within 4 weeks before randomization. * Use of immunosuppressive medication or biologic or immunomodulatory therapy within 5 half-lives before randomization. * Pregnancy or lactation. * For participants of childbearing potential, unwillingness to use effective contraception during the 24-week blinded intervention period. * Severe psychiatric illness or cognitive impairment that, in the investigator's judgment, would impair informed consent, participant safety, or adherence to study procedures. * Active eating disorder, defined as at least 2 affirmative responses on the SCOFF screening questionnaire or a clinical diagnosis of anorexia nervosa, bulimia nervosa, or binge-eating disorder. * Heavy alcohol use or active substance use disorder. * Current use of a very-low-calorie diet, ketogenic diet, medically supervised weight-loss diet, or another highly restrictive diet that excludes major food groups. * Current cigarette smoking with a stated intention to attempt smoking cessation during the 24-week study, or initiation of nicotine-replacement or other smoking-cessation pharmacotherapy within 3 months before randomization. * Participation in another interventional clinical study within 30 days before screening. * Known hypersensitivity or clinically significant intolerance to any component of the active supplement or placebo. * Any condition that, in the investigator's judgment, would compromise participant safety, adherence, or study integrity.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Body Weight From Baseline to Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Body Weight From Baseline to Week 24 | 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. |
| Proportion of Participants Achieving at Least 5% Body-Weight Loss at Week 12 | Baseline to 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. |
| Change in Waist Circumference From Baseline to Week 12 | 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. |
| Proportion of Participants Achieving at Least 5% Body-Weight Loss at Week 24 | Baseline to 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. |
| Change in Waist Circumference From Baseline to Week 24 | 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. |
| Change in Gut Microbiome Shannon Diversity Index From Baseline to Week 12 | 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. |
| Change in Gut Microbiome Community Composition From Baseline to Week 12 | 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. |
Countries
Turkey (Türkiye)
Contacts
STUDY_DIRECTORVarol TUNALI, Dr.
Enbiosis Biotechnology Limited
Outcome results
None listed