AIM-WEIGHT: AI-Guided Microbiome-Targeted Nutritional Intervention for Weight Loss

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.

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.