GENETIC VARIABILITY TO GLP1 TREATMENT (GLP1 treatment)

RETRO-PROSPECTIVE OPEN STUDY TO ASSES GENETIC VARIABILITY AS A BASIS FOR PREDICTION OF THE RESPONSE TO GLP1 TREATMENT

The goal of this retrospective study is to assess whether a selection of genetic variants may allow us to identify individuals who will have a satisfactory response after GLP-1 treatment in terms of weight loss, sugar level reduction, and adverse events.

Participants will The study consists of a single visit at the diabetes unit clinic at the involved study sites. The following will be performed for every subject at the study screening enrollment visit:

• Informed consent
• Study eligibility (Inclusion / Exclusion criteria)
• Collection of demographic data (age (date of birth), gender, ethnic origin)
• General and T2DM medical history review (per subject file)
• Concomitant medication review (at enrollment)
• Physical attributes (Body Weight, Height, BMI)
• Allocation to study cohort and study subgroup
• Saliva and blood collection for genetic tests
• Self-reported questionnaire for Ozempic (Semaglutide) experience

Study Overview

• Status: Recruiting
• Conditions: Obesity; Type 2 Diabetes
• Intervention / Treatment: Genetic: DNA Sequencing and Analysis; Genetic: differential expression analysis with RNA-sequencing (RNA seq) experiments

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hila Kfir; Phone Number: +972-523313350; Email: hilaz28@gmail.com
• Study Contact Backup: Name: Ilana Reznikov; Email: Reznikovilana@gmail.com

Study Locations

• Israel
  • Haifa, Israel
    • Recruiting
    • Rambem medical center
    • Principal Investigator: Irit Hochberg, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Diagnosed with type 2 diabetes (for participant in Cohort A) or Obese (for participant in Cohort B) and treated with Ozempic (Semaglutide) S.C. injection for at least 24 weeks.
2. Subject is male/female between 18 to 80 years old (both inclusive) at the time of enrollment.
3. Subject BMI above 30 kg/m2 at treatment initiation.
4. Subject does not belong to any vulnerable population, is willing and able to provide written informed consent prior to any study procedure.
5. Participant understands the nature of the procedure and is willing and able to comply with all requirement of the protocol.

Exclusion Criteria:

1. Subject falls under contraindications to Ozempic (Semaglutide) label
2. Subject known or suspected for hypersensitivity to any GLP-1RA or related products, or allergic constitution
3. Subjects suffers from any other condition affecting body weight.
4. Subject with history of chronic or acute pancreatitis
5. Subject have a history of a major cardiovascular and/or cerebrovascular disease within the 6 months before screening.
6. Presence or history of malignant neoplasm within 5 years prior to screening day.
7. Subject suffers from any renal impairment (Cr > 2 mg/dl).
8. Subject suffers from any impaired hepatic function (ALT, AST or GGT 2-fold higher than normal upper limit).
9. Any disorder, which in the investigator's opinion might jeopardize patient's safety or compliance with the protocol.
10. Subject is a female who is pregnant, breastfeeding or intends to become pregnant or is of child bearing potential without medically acceptable methods of contraception.
11. Participation in another clinical study in prior 4 weeks.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Collection of DNA/RNA samples; Type 2 Diabetic participants cohort or Healthy participants cohort who will perform Collection of DNA/RNA samples

Genetic: DNA Sequencing and Analysis; DNA extracted from saliva / oral mucosa will be tested for diversities reported in the literature known to be associated with T2DM and Obesity and which may have a potential impact on the response to treatment with Semaglutide. In addition, the DNA will be screened for new diversities that have a potential impact on the response to treatment. working assumption of the study is that there can be 3 types of genetic variants that affect the drug's effectiveness and/or side effects.; Genetic: differential expression analysis with RNA-sequencing (RNA seq) experiments; Performing small RNA sequencing experiments on an Illumina Next-Generation Sequencing (NGS) machine to investigate microRNAs (miRNAs) or other small non-coding RNAs involves specific steps tailored to the unique characteristics of these molecules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic variants and miRNA expressions associated with changes in BMI.	Identify genetic variants and miRNA expressions that affects the response to GLP-1 treatment associated with changes in BMI.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic variants and miRNA expressions associated with changes in A1c.	Identify genetic variants and miRNA expressions that affects the response to GLP-1 treatment associated with changes in A1c.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic variants and miRNA expressions associated with side effects.	Identify genetic variants and miRNA expressions that affects the response to GLP-1 treatment associated with side effects.	12 months
Demographic parameters that affect GLP1 AG therapy.	To identify demographic parameters that affect the response to GLP1 AG therapy.	12 months

Collaborators and Investigators

• Sponsor: GENGE

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2023
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: March 1, 2024
• First Submitted That Met QC Criteria: March 1, 2024
• First Posted (Actual): March 7, 2024

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: GEN-GE-001-IL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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