Development of a Genetic Score as a Response Modifier for Changes in Weight, Body Composition, and Biochemical Parameters in Obese Adults Undergoing a Low-Energy High-Protein Diet Intervention (Gens-HiPro)

The goal of this clinical trial is to evaluate whether a genetic score (Gens-HiPro) acts as a response modifier for weight loss, body composition changes, and biochemical parameters in obese adults undergoing a low-energy high-protein diet intervention.

The main questions it aims to answer is:

Does the genetic score (Gens-HiPro) modify responses to changes in weight, body composition, and biochemical parameters following a 12-week low-energy high-protein diet?

Participants will:

• Undergo initial screening to determine eligibility based on inclusion and exclusion criteria
• Complete baseline data measurement, including demographic data, anthropometric measurements (weight, BMI, body composition), biochemical blood analysis (total cholesterol, triglycerides, HDL, LDL, CRP), dietary assessment.
• Attend a small-group educational session on general guidelines, portion control, plate model ("Isi Piringku"), and food weighing techniques for a low-energy high-protein diet.
• Receive a 60-90 minute nutritional counseling session led by a dietitian at the start of intervention
• Follow the prescribed 12-week low-energy high-protein diet, supported by an active messaging channel on weekdays for daily dietary consultations
• Participate in at least three in-person monitoring and evaluation visits scheduled every 3-4 weeks (at weeks 4, 8, and 12 or weeks 4, 7, 10 and 12)
• Complete post-intervention evaluations at the end of week 12, repeating all baseline anthropometric, biochemical, and dietary assessments.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity
• Intervention / Treatment: Behavioral: Low-Energy High-Protein Diet

Detailed Description

Subjects will be stratified or analyzed based on their genetic profile using the Gens-HiPro score to evaluate gene-diet interactions on weight loss outcomes. Gens-HiPro Genetic Score: A genetic risk score calculated as the sum of the products of each selected single nucleotide variant's (SNV) allele score and its respective effect size (mean difference [MD] in weight loss between allele groups). The selected genetic variants were screened and identified through a systematic review and meta-analysis, including: APOA1 rs670, CB2R/CNR2 rs3123554, FTO rs1421085, FTO rs9939609, MC4R rs17782313, and MTNR1B rs10830963. An allele score of 0 is assigned if a specific genetic variant falls into the genotype group with a smaller mean difference in weight loss. An allele score of 1 is assigned if the variant falls into the genotype group with a larger mean difference. The effect size represents the mean difference in weight loss, calculated by subtracting the mean weight loss of the genotype group with the smaller MD from the mean weight loss of the genotype group with the larger MD.

• Study Type: Interventional
• Enrollment (Estimated): 29
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yovita Puri Subardjo, S.Gz., Dietisien, MPH; Phone Number: +628174100488; Email: yovitapurisubardjo@mail.ugm.ac.id

Study Locations

• Indonesia
  • Central Java
    • Banyumas, Central Java, Indonesia, 53122
      • Integrated Health Science Building, Faculty of Health Sciences
      • Contact: Adendita Azmi Afiattami, S.Gz; Phone Number: +6285117481147; Email: adendita.azmi@unsoed.ac.id

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult males or females aged 18 - 40 years.
• Classified as obese with a Body Mass Index (BMI) of 27 - 35 kg/m² and a waist circumference of ≥90 cm for men and ≥80 cm for women.
• Willing to adhere to the prescribed low-energy high-protein diet.
• Willing to undergo anthropometric measurements, body composition analysis, lipid profile testing, and genetic variation screening.
• Signed the written informed consent form.

Exclusion Criteria:

• Having chronic diseases that affect metabolism or body weight.
• Diagnosed with chronic kidney disease (CKD).
• Currently pregnant, lactating, or planning a pregnancy during the study period.
• Currently participating in an intensive weight loss program or receiving pharmacological therapy for weight loss within the last 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: low-energy high-protein diet intervention; Participants in this single-arm study will undergo a 12-week low-energy high-protein diet intervention (personalized nutritional counseling by a dietitian).

Behavioral: Low-Energy High-Protein Diet; This intervention consists of a 12-week low-energy high-protein diet program delivered through structured behavioral and nutritional counseling. Nutrition care process: individual nutritional counseling, one-on-one counseling session conducted by a registered dietitian. The dietary regimen is prescribed with an energy deficit of 500-750 kcal/day, ensuring a minimum daily energy intake of 1.200 kcal/day for women and 1.500 kcal/day for men. Macronutrient distribution is targeted at 1.2-1.6 g/kg adjusted body weight for protein, 20-30% of total energy for fat, and 45-55% of total energy for carbohydrates. Genetic profiling using the Gens-HiPro score is conducted to evaluate its role as a modifier of outcome responses in weight loss, body composition, and biochemical parameters.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Weight	Body weight refers to the total body mass of the subject, measured using a weighing scale in kilograms (kg). The change in body weight is calculated as the difference between the body weight value at the baseline of the intervention (Week 0) and the end of the intervention (Week 12). (Scale: Ratio)	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Mass Index (BMI)	Body Mass Index is the ratio of the subject's body weight in kilograms divided by the square of their height in meters (kg/m²). The change in BMI is calculated as the difference between the BMI value at the baseline of the intervention (Week 0) and the end of the intervention (Week 12). (Scale: Ratio)	12 weeks
Change in Fat Mass	Fat mass is the total amount of fat present in the subject's body, measured using Bioelectrical Impedance Analysis (BIA). The change in fat mass is calculated as the difference between the fat mass value in kg at the baseline of the intervention (Week 0) and the end of the intervention (Week 12). (Scale: Ratio)	12 weeks
Change in Muscle Mass	Muscle mass refers to the total amount of muscle (skeletal muscle mass) in the subject's body, measured using Bioelectrical Impedance Analysis (BIA). The change in muscle mass is calculated as the difference between the muscle mass value in kg at the baseline of the intervention (Week 0) and the end of the intervention (Week 12). (Scale: Ratio)	12 weeks
Change in Visceral Fat	isceral fat is the fat stored within the abdominal cavity that surrounds the subject's internal organs, measured using Bioelectrical Impedance Analysis (BIA). The change in visceral fat mass is calculated as the difference between the visceral fat mass value at the baseline of the intervention (Week 0) and the end of the intervention (Week 12). (Scale: Ratio)	12 weeks
Change in Waist Circumference	Waist circumference is a simple physical measurement taken using a measuring tape (metline) around the abdomen to estimate central obesity, reported in centimeters (cm). The change in waist circumference is calculated as the difference between the waist circumference value at the baseline of the intervention (Week 0) and the end of the intervention (Week 12). (Scale: Ratio)	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fasting Serum Triglycerides	Triglycerides refer to triacylglycerol molecules, measured via biochemical analysis of blood after a minimum 8-hour fast and reported in mg/dL. The change in triglyceride values is calculated as the difference between the triglyceride value at the baseline of the intervention (Week 0) and the end of the intervention (Week 12). (Scale: Ratio)	12 weeks
Change in Fasting Serum High-Density Lipoprotein (HDL) Cholesterol	HDL refers to small plasma lipoprotein particles, measured via biochemical analysis of blood after a minimum 8-hour fast and reported in mg/dL. The change in HDL values is calculated as the difference between the HDL value at the baseline of the intervention (Week 0) and the end of the intervention (Week 12). (Scale: Ratio)	12 weeks
Change in Fasting Serum Low-Density Lipoprotein (LDL) Cholesterol	LDL refers to low-density plasma lipoprotein particles, measured via biochemical analysis of blood after a minimum 8-hour fast and reported in mg/dL. The change in LDL values is calculated as the difference between the LDL value at the baseline of the intervention (Week 0) and the end of the intervention (Week 12). (Note: Fixed a typo in your original text which stated "nilai HDL pada awal intervensi"). (Scale: Ratio)	12 weeks
Change in Fasting Serum Total Cholesterol	Total cholesterol is the concentration of all cholesterol contained within the lipoproteins circulating in the blood, measured enzymatically in serum/plasma and reported in mg/dL. The change in total cholesterol values is calculated as the difference between the total cholesterol value at the baseline of the intervention (Week 0) and the end of the intervention (Week 12). (Scale: Ratio)	12 weeks
Change in High-Sensitivity C-Reactive Protein (hs-CRP)	CRP is the measured concentration of an acute-phase protein produced by the liver in response to inflammatory cytokines, measured using a standard hs-CRP assay and reported in mg/dL. The change in CRP values is calculated as the difference between the CRP value at the baseline of the intervention (Week 0) and the end of the intervention (Week 12). (Scale: Ratio)	12 weeks

Collaborators and Investigators

• Sponsor: Gadjah Mada University
• Collaborators: Universitas Jenderal Soedirman; Faculty of Medicine, Gadjah Mada University

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: August 7, 2026
• First Submitted That Met QC Criteria: August 7, 2026
• First Posted (Actual): August 12, 2026

Study Record Updates

• Last Update Posted (Actual): August 13, 2026
• Last Update Submitted That Met QC Criteria: August 11, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: obesity; nutrigenetics; genetic variation; low-energy high-protein diet; genetic score; gens-hipro
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity
• Other Study ID Numbers: 092/KEPK/PE/VII/2026 (Other Identifier: Health Research Ethics Committee, Faculty of Medicine, Universitas Jenderal Soedirman); 202406210804017 (Other Grant/Funding Number: Indonesia Endowment Fund for Education Agency (LPDP RI)); 548/UN1/FKKMK.3/S3KK.3/PJ/2026 (Other Identifier: Doctoral Program in Medical and Health Sciences, Faculty of Medicine, Public Health, and Nursing UGM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared to protect patient privacy and confidentiality, in accordance with the informed consent signed by the participants and the restrictions set by the Institutional Review Board (IRB) / Ethics Committee.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No