Semaglutide in CFRD

Study Overview
=================
Brief Summary
-----------------
This open label, single arm pilot study, will examine the safety and tolerability of GLP-1RA semaglutide as an add-on therapy to insulin for overweight/obese adult patients with cystic fibrosis related diabetes (CFRD).

Detailed Description
-----------------
The overall goal of this proposal is to collect pilot data for safety and feasibility metrics to support a future larger randomized controlled trial. In this study, we will examine the safety and tolerability of GLP-1RA semaglutide as an add-on therapy to insulin for overweight/obese adult patients with CFRD. We hypothesize that weekly administration of the long-acting GLP-1RA semaglutide to overweight/obese CFRD patients will be safe and well tolerated. Specific Aim 1: Collect pilot data on the safety and feasibility of weekly semaglutide therapy in overweight and obese patients with CFRD to support a future larger randomized controlled trial. Hypothesis 1: Weekly therapy with GLP-1RA semaglutide will be safe and well tolerated in overweight/obese adults with CFRD. Specific Aim 2: Collect preliminary data to examine the impact of semaglutide therapy on insulin secretion, glucagon and glucose levels as measured by oral glucose tolerance test (OGTT), and on glycemic outcomes as measured by continuous glucose monitoring (CGM) and HbA1c. Hypothesis 2a: Treatment with semaglutide will lower glucose levels, and increase insulin and C-peptide area under the curve (AUC) during the OGTT as compared to baseline. Hypothesis 2b: Treatment with semaglutide will improve glycemic control as indicated by time in range on CGM and HbA1c

Official Title
-----------------
Efficacy and Safety of GLP-1 Agonist Therapy in Overweight and Obese Subjects With Cystic Fibrosis-related Diabetes: a Pilot Study

Conditions
-----------------
Cystic Fibrosis, Cystic Fibrosis-related Diabetes

Intervention / Treatment
-----------------
* Drug: Semaglutide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult subjects 18 years or older with CFRD and on insulin treatment BMI >26 kg/m2 Diagnosis of pancreatic insufficiency (based on treatment with pancreatic enzyme replacement therapy) A participant who is capable of becoming pregnant must agree to take precautions that are effective in preventing pregnancy throughout this study. These methods could include one of the following 1. Complete abstinence from sexual intercourse; 2. Oral, injectable, or implanted hormonal contraceptives 3. Intrauterine device 4. Tubal ligation Exclusion Criteria: personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN2) acute pulmonary exacerbation requiring IV antibiotics or systemic glucocorticoids within 4 weeks prior to baseline study procedures gastrointestinal(GI) symptom exacerbation defined by current nausea/vomiting or diarrhea at the baseline assessment history of chronic GI problems requiring hospitalization in the 1 year prior to baseline history of clinically symptomatic pancreatitis history of clinically significant gastroparesis history of eating disorders less than 24 weeks since start of a new CFTR corrector/modulator therapy pregnancy or lactation severe CF liver disease chronic kidney disease history of suicide attempts or active suicidal ideation Non-English speakers and those unable to read in English

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This open label, single arm pilot study, will examine the safety and tolerability of GLP-1RA semaglutide as an add-on therapy to insulin for overweight/obese adult patients with CFRD.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Single Arm<br>This open label, single arm pilot study, will examine the safety and tolerability of GLP-1RA semaglutide as an add-on therapy to insulin for overweight/obese adult patients with CFRD. | Drug: Semaglutide<br>* glucagon-like peptide 1 (GLP-1) receptor agonist<br>* Other names: Semaglutide Injectable Product;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility, safety, tolerability | The primary outcomes are related to feasibility, including safety and treatment tolerability. Safety will be evaluated as the proportion (in %) of participants who experience a serious adverse event during the study. Tolerability will be evaluated as the proportion (in %) of participants who discontinue their assigned treatment due to side effects. | Duration of anticipated participation for an individual participant's would be around 15 weeks.Duration anticipated to complete all study procedures, including any long-term follow-up, and data analysis is 24 months. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CFRD