Nutritional Therapy to Incretin-based Anti-obesity Medications in the Management of Gastrointestinal Adverse Events

Adjuvant Nutritional Therapy to Incretin-based Anti-obesity Medications in the Management of Gastrointestinal Adverse Events During the Up-titration Phase

The goal of the study is to evaluate the effect of nutrition intervention on gastrointestinal symptoms, treatment discontinuation rate, nutritional parameters (e.g., dietary intake and eating habits), anthropometric measures, functional parameters, and QOL during the initiation and up-titration phase of incretin-based Anti Obesity Medications (AOM) treatment in patients with overweight/obesity.

The nutrition intervention protocol will be developed based on literature review, focus groups with health care professionals, and patient interviews.

A single-center pilot study will be performed at the Tel-Aviv Assuta Medical Center, among 10 patients who are about to initiate long-term weight management treatment with Wegovy© (semaglutide 2.4 mg), followed by a multi-center, parallel design open-label, RCT, which will be conducted at the Tel-Aviv Assuta Medical Center and Rabin Medical Center - Beilinson Hospital, in 120 patients who are about to initiate long-term weight management treatment with Wegovy© or Mounjaro© .

The intervention group will receive nutrition guidance before AOM treatment by registered dietitian (RD) followed by nutrition and behavioral recommendations according to reported gastrointestinal symptom(s). The control group will receive the usual nutrition care for patients treated with AOM.

Primary outcomes (gastrointestinal symptom assessment) and secondary outcomes (incretin-based AOM discontinuation rate, nutritional parameters, anthropometrics, functional parameters and QOL) will be evaluated by interviews, questionnaires and measurements at baseline, at the end of Wegovy© or Mounjaro© titration phase [20 weeks (T1)] and weekly during the study period (for GI symptoms assessment).

Study Overview

• Status: Recruiting
• Conditions: Obesity; Drug
• Intervention / Treatment: Behavioral: nutritional intervention

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shiri Sherf-dagan, Ph.D; Phone Number: +972747288004; Email: shiris@ariel.ac.il
• Study Contact Backup: Name: Rotem Refaeli; Phone Number: +972545797995; Email: rotem2310@gmail.com

Study Locations

• Israel
  • Ariel, Israel, 40700
    • Recruiting
    • Ariel University
    • Contact: Shiri Sherf-Dagan, PhD; Phone Number: +972525122203; Email: shiris@ariel.ac.il
  • Petah Tikva, Israel, 4941492
    • Not yet recruiting
    • Rabin Medical Center, Beilinson Hospital
    • Contact: Rotem Refaeli; Phone Number: 0545797995; Email: rotem2310@gmail.com
    • Contact: Matan Lifshitaz; Phone Number: 05422888699; Email: matanlif2@gmail.com
    • Sub-Investigator: Rotem Refaeli
  • Tel Aviv, Israel, 6971028
    • Recruiting
    • Assuta Medical Center
    • Contact: Shiri Sherf-Dagan, Dr; Phone Number: +972-52-5122203; Email: shirishe@assuta.co.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• individuals aged ≥ 18 years
• eligible to receive AOM [i.e., BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with at least one adiposity-related coexisting condition (e.g., diabetes or pre-diabetes, hypertension, dyslipidemia, obstructive sleep apnea, fatty liver, cardiovascular disease)]
• who can read and speak Hebrew.

Exclusion Criteria:

• Contraindications or precautious for treatment with Wegovy© or Mounjaro© [i.e., personal or family history of medullary thyroid cancer (MTC), personal history of multiple endocrine neoplasia type 2 (MEN2) syndrome, attempting conception, current pregnancy or breastfeeding]
• previous bariatric surgery or endo-bariatric procedure
• presence of chronic pancreatitis
• treatment with AOM within a month before enrollment
• patients with type 1 diabetes mellitus
• patients who underwent other major GI surgery prior to medication treatment
• patient with underlying GI disease [e.g., gastroparesis, celiac, Inflammatory Bowel Disease (IBD)]
• a positive diagnosis of small-intestinal bacterial overgrowth (SIBO)
• patients with active gastritis, gastroenteritis
• chronic usage of promotility drugs or laxatives
• patients with uncontrolled mental illness
• significant cognitive deterioration
• alcohol consumption exceeding 1 drink per day for women and 2 drinks per day for men .

In addition, participants who decide not to initiate or stop Wegovy© or Mounjaro© treatment for more than two consecutive injections for any reason or who undergo bariatric surgery or endoscopic sleeve gastroplasty during the study period will be excluded from the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nutritional intervention group; Nutrition guidance before AOM treatment by registered dietitian (RD) followed by nutrition and behavioral recommendations according to reported gastrointestinal symptom(s).	Behavioral: nutritional intervention; A nutrition guidance before initiation of AOM treatment include recommendations for food choices and eating habits to minimize the occurrence and severity of GI symptoms during the up-titration phase, will be given by registered dietitian (RD) from the study team. Next, each week, participants will provide weekly reports of GI symptoms occurrence and severity, by responding to queries sent via WhatsApp/SMS and for occurring symptoms, an automatically structured nutrition and behavioral treatment recommendations will be sent . If participants expressed an interest in personalized dietary guidance on this matter, the study team RD will contact him/her by telephone, within a range of 48 hours, to provide individualized recommendations. Three days after each report of GI symptom(s), participants will receive an additional message and will be asked to report the occurrence and severity of the GI symptom, and their compliance with the specific dietary instructions received.
No Intervention: Control group; Usual nutrition care treatment for patients treated with Wegovy© or Mounjaro© (RCT).; Prior to the initiation of AOM treatment, participant will receive general nutrition guidance based on national recommendations according to the Mediterranean diet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastrointestinal symptoms assessment	GI symptoms rating scale (GSRS) - assess the degree of specific GI complaints Every question is rated by seven graded Likert-type scale (1 represents the absence of troublesome symptoms and 7 represents very troublesome symptoms) while a higher score of the whole questionnaire and by dimension represents more severe symptoms.	Baseline and at the end of the study period (20 weeks)
Defecation texture	Bristol stool scale - classifying the form of human feces into seven categories. Type 1-2 are considered abnormal hard stools and indicative of constipation type, and type 5-7 are considered abnormally loose/liquid stools and indicative of diarrhea or urgency	Baseline and at the end of the study period (20 weeks)
Bowel Movement (BM) frequency	will be assessed according to five acceptable categories: >3 BMs/day, 2-3 BMs/day, 1-2 BMs/day, 3-4 BMs/week, <3 BMs/week	Baseline and at the end of the study period (20 weeks)
Participants gastrointestinal symptoms report	Participant subjective and objective reporting of GI symptoms	Baseline, at the end of the study period (20 weeks) and weekly until 20 weeks (for subjective GI symptoms report only)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incretin-based AOM treatment discontinuation rate		At the end of the study period (20 weeks) and weekly until 20 weeks
Anthropometric measures - waist circumference (WC)	will be measured by tape measure (cm)	Change from baseline at the end of the study period (20 weeks)
Eating habits assessment	General questions regarding eating patterns, hydration and foods intolerance	Change from baseline at the end of the study period (20 weeks)
Eating habits assessment - Control of Eating	Control of Eating Questionnaire (CoEQ) - The of CoEQ consists of 21 items (19 questions are rated by 100 mm VAS, and two question are open-ended). Greater score represents greater levels of Craving Control.	Change from baseline at the end of the study period (20 weeks)
Functional parameters - muscle strength	Handgrip (HG) muscle Strength - measure static muscle strength (kg) of the upper extremities by a digital hand dynamometer (Jamar plus digital©)	Change from baseline at the end of the study period (20 weeks)
Functional parameters- leg strength and endurance	30-seconds sit and stand test - counts the number of times the patient stands in 30 seconds. Higher scores means a better outcome.	Change from baseline at the end of the study period (20 weeks)
Quality of life assessment	EQ-5D-3L questionnaire -include the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS) .The EQ-5D-3L descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems.The EQ VAS records the patient's self-rated health. Participants will be asked to subjectively rate their overall state of health by using a 0 to 100 VAS, with a higher score reflects a better outcome.	Change from baseline at the end of the study period (20 weeks)
Anthropometric measures - weight	Weight (kg) by digital scale	Change from baseline at the end of the study period (20 weeks)
Body composition - fat mass (kg)	Body composition analysis using Inbody370S®	Change from baseline at the end of the study period (20 weeks)
Dietary intake	24-hour dietary recall (24HR)	Change from baseline at the end of the study period (20 weeks)
Eating habits assessment - Food preferences	Leeds Food Preference Questionnaire (LFPQ). The questionnaire involves an explicit evaluation of "liking" and "wanting" for 16 food items that can be categorized as high-fat savory (HFSA), low-fat savory (LFSA), high-fat sweet (HFSW) and low-fat sweet (LFSW). Each food image is scored on a 100-mm VAS, while a higher score indicates a stronger preference for that food category. The second sub-task evaluates "implicit wanting" and requires rapid choice between 96 paired combinations of the food images from different categories	Change from baseline at the end of the study period (20 weeks)
Anthropometric measures - height (cm)	(cm) by altimeter	Change from baseline at the end of the study period (20 weeks)
Body composition- percentage of body fat (BF%)	Body composition analysis using Inbody370S®	Change from baseline at the end of the study period (20 weeks)
Body composition - fat-free mass (kg)	Body composition analysis using Inbody370S®	Change from baseline at the end of the study period (20 weeks)
Body composition - skeletal muscle mass (kg)	Body composition analysis using Inbody370S®	Change from baseline at the end of the study period (20 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Demographics - age	years	At baseline
Demographics - marital status	married, single, divorced or widowed	At baseline
Demographics - education	less than high school, high school graduate, high school diploma, bachelors degree, masters degree, MD or doctoral degree	At baseline
Demographics - occupation status	employee full time, employee part time, self-employed or other	At baseline
Health status - Number of participants with coexisting medical conditions and their types	T2DM, prediabetes, dyslipidemia, HTN,sleep apnea, orthopedic problems, GERD, mental disorder or other	Baseline and at the end of the study period (20 weeks)
Number of participants using regular medications and their types	usual medications	Baseline and at the end of the study period (20 weeks)
Smoking habits	smoker, former smoker or never	Baseline and at the end of the study period (20 weeks)
Lifestyle factors - Sleeping habits	sleeping quality on a scale of 0-3 (0- very good, 1-quite good, 2- quite bad, 3- very bad)	Baseline and at the end of the study period (20 weeks)
Lifestyle factors - frequency of physical activity	number of exercises per week	Baseline and at the end of the study period (20 weeks)
Lifestyle factors - duration of physical activity	exercise time in minutes	Baseline and at the end of the study period (20 weeks)
Lifestyle factors - type of physical activity	aerobic or anaerobic	Baseline and at the end of the study period (20 weeks)
Biochemical tests	Participants will be asked to provide at T0 biochemical tests obtained during the last 3 months, including complete blood count, lipid profile, fasting glucose, HbA1c, iron, transferrin, ferritin, vitamin B12, folate, vitamin D, albumin and total protein	At baseline
Number of participants using supplementation and their Types	multiviamin, Iron, vitamin D, folic acid, vitamin B12, calcium or other	Baseline and at the end of the study period (20 weeks)

Collaborators and Investigators

• Sponsor: Ariel University

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2025
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): March 30, 2026

Study Registration Dates

• First Submitted: March 28, 2024
• First Submitted That Met QC Criteria: May 26, 2024
• First Posted (Actual): May 28, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2025
• Last Update Submitted That Met QC Criteria: April 21, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Obesity
• Other Study ID Numbers: ASMC-0003-24

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No