## Protocol Section
### Identification Module
**NCT ID:** NCT06431308

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

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

#### Organization Study ID Info
**ID:** ASMC-0003-24
#### Organization
**Class:** OTHER
**Full Name:** Ariel University
### Status Module
#### Completion Date
**Date:** 2026-04-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-28

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-26

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-04-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-28
**Type:** ACTUAL
**Study First Submit Date:** 2024-03-28
**Study First Submit QC Date:** 2024-05-26
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Ariel University

#### Responsible Party

**Investigator Affiliation:** Ariel University

**Investigator Full Name:** Shiri Sherf Dagan

**Investigator Title:** Principal Investigator

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**Brief Summary:** 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©.

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© titration phase \[20 weeks (T1)\] and weekly during the study period (for GI symptoms assessment).

### Conditions Module

**Conditions:**

- Obesity; Drug

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 120

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Nutrition guidance before AOM treatment by registered dietitian (RD) followed by nutrition and behavioral recommendations according to reported gastrointestinal symptom(s).

**Intervention Names:**

- Behavioral: nutritional intervention

**Label:** Nutritional intervention group

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** * Usual nutrition care treatment for patients treated with Wegovy© (RCT).
* Prior to the initiation of AOM treatment, participant will receive general nutrition guidance based on national recommendations according to the Mediterranean diet.

**Label:** Control group

**Type:** NO_INTERVENTION

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Nutritional intervention group

**Description:** 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. 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. 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

**Name:** nutritional intervention

**Type:** BEHAVIORAL

### Outcomes Module

#### Other Outcomes

**Description:** 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, and vitamin D

**Measure:** Biochemical tests

**Time Frame:** At baseline

**Description:** years

**Measure:** Demographics - age

**Time Frame:** At baseline

**Description:** married, single, divorced or widowed

**Measure:** Demographics - marital status

**Time Frame:** At baseline

**Description:** less than high school, high school graduate, high school diploma, bachelors degree, masters degree, MD or doctoral degree

**Measure:** Demographics - education

**Time Frame:** At baseline

**Description:** employee full time, employee part time, self-employed or other

**Measure:** Demographics - occupation status

**Time Frame:** At baseline

**Description:** T2DM, prediabetes, dyslipidemia, HTN,sleep apnea, orthopedic problems, GERD, mental disorder or other

**Measure:** Health status - Number of participants with coexisting medical conditions and their types

**Time Frame:** Baseline and at the end of the study period (20 weeks)

**Description:** usual medications

**Measure:** Number of participants using regular medications and their types

**Time Frame:** Baseline and at the end of the study period (20 weeks)

**Description:** smoker, former smoker or never

**Measure:** Smoking habits

**Time Frame:** Baseline and at the end of the study period (20 weeks)

**Description:** multiviamin, Iron, vitamin D, folic acid, vitamin B12, calcium or other

**Measure:** Number of participants ysing supplementation and their Types

**Time Frame:** Baseline and at the end of the study period (20 weeks)

**Description:** sleeping quality on a scale of 0-3 (0- very good, 1-quite good, 2- quite bad, 3- very bad)

**Measure:** Lifestyle factors - Sleeping habits

**Time Frame:** Baseline and at the end of the study period (20 weeks)

**Description:** number of exercises per week

**Measure:** Lifestyle factors - frequency of physical activity

**Time Frame:** Baseline and at the end of the study period (20 weeks)

**Description:** exercise time in minutes

**Measure:** Lifestyle factors - duration of physical activity

**Time Frame:** Baseline and at the end of the study period (20 weeks)

**Description:** aerobic or anaerobic

**Measure:** Lifestyle factors - type of physical activity

**Time Frame:** Baseline and at the end of the study period (20 weeks)

#### Primary Outcomes

**Description:** 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.

**Measure:** Gastrointestinal symptoms assessment

**Time Frame:** Baseline and at the end of the study period (20 weeks)

**Description:** 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

**Measure:** Defecation texture

**Time Frame:** Baseline and at the end of the study period (20 weeks)

**Description:** 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

**Measure:** Bowel Movement (BM) frequency

**Time Frame:** Baseline and at the end of the study period (20 weeks)

**Description:** Participant subjective and objective reporting of GI symptoms

**Measure:** Participants gastrointestinal symptoms report

**Time Frame:** Baseline, at the end of the study period (20 weeks) and weekly until 20 weeks (for subjective GI symptoms report only)

#### Secondary Outcomes

**Measure:** Incretin-based AOM treatment discontinuation rate

**Time Frame:** At the end of the study period (20 weeks) and weekly until 20 weeks

**Description:** Weight (kg) by digital scale, height (cm) by altimeter. weight and height will be combined to report BMI in kg/(meter)\^2

**Measure:** Anthropometric measures - BMI

**Time Frame:** Change from baseline at the end of the study period (20 weeks)

**Description:** will be measured by tape measure (cm)

**Measure:** Anthropometric measures - waist circumference (WC)

**Time Frame:** Change from baseline at the end of the study period (20 weeks)

**Description:** Body composition analysis using Inbody370S® includes measuring of fat mass (kg) , percentage of body fat (BF%), fat-free mass (kg), and skeletal muscle mass (kg).

**Measure:** Body composition

**Time Frame:** Change from baseline at the end of the study period (20 weeks)

**Description:** 3-days food diaries and Israeli Ministry of Health Food Frequency Questionnaire (FFQ) that will be modified for the current study population

**Measure:** Dietary intake

**Time Frame:** Change from baseline at the end of the study period (20 weeks)

**Description:** General questions regarding eating patterns, hydration and foods intolerance

**Measure:** Eating habits assessment

**Time Frame:** Change from baseline at the end of the study period (20 weeks)

**Description:** 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.

**Measure:** Eating habits assessment - Control of Eating

**Time Frame:** Change from baseline at the end of the study period (20 weeks)

**Description:** Handgrip (HG) muscle Strength - measure static muscle strength (kg) of the upper extremities by a digital hand dynamometer (Jamar plus digital©)

**Measure:** Functional parameters - muscle strength

**Time Frame:** Change from baseline at the end of the study period (20 weeks)

**Description:** 30-seconds sit and stand test - counts the number of times the patient stands in 30 seconds. Higher scores means a better outcome.

**Measure:** Functional parameters- leg strength and endurance

**Time Frame:** Change from baseline at the end of the study period (20 weeks)

**Description:** 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.

**Measure:** Quality of life assessment

**Time Frame:** Change from baseline at the end of the study period (20 weeks)

### Eligibility Module

**Eligibility Criteria:** 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 for treatment with Wegovy© \[i.e., personal or family history of medullary thyroid cancer (MTC), personal history of multiple endocrine neoplasia type 2 (MEN2) syndrome, a history of acute pancreatitis from an unknown etiology, attempting conception, current pregnancy or breastfeeding\]
* previous bariatric surgery or endo-bariatric procedure
* history of chronic pancreatitis
* treatment with AOM within 6 months 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 (32).

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

**Healthy Volunteers:** True

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** shiris@ariel.ac.il

**Name:** Shiri Sherf-dagan, Ph.D

**Phone:** +972747288004

**Role:** CONTACT

**Contact 2:**

**Email:** rotem2310@gmail.com

**Name:** Rotem Refaeli

**Phone:** +972545797995

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Ariel

**Country:** Israel

**Facility:** Ariel University

**Zip:** 40700

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000050177

- Term: Overweight

- ID: D000044343

- Term: Overnutrition

- ID: D000009748

- Term: Nutrition Disorders

- ID: D000001835

- Term: Body Weight

### Condition Browse Module - Browse Branches

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M12701

- Name: Obesity

- Relevance: HIGH

- As Found: Obesity

- ID: M26186

- Name: Overweight

- Relevance: LOW

- As Found: Unknown

- ID: M25307

- Name: Overnutrition

- Relevance: LOW

- As Found: Unknown

- ID: M12684

- Name: Nutrition Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M5114

- Name: Body Weight

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000009765

- Term: Obesity

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M27905

- Name: Incretins

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
