SGLT2 Inhibitor Therapy in Cystic Fibrosis-related Diabetes

Study Overview
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Brief Summary
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This will be a placebo-controlled, randomized, double blind, crossover study with a 4 week wash out period. Collect pilot data on the safety, tolerability, and feasibility of empagliflozin therapy in overweight/obese patients with CFRD to support a future larger randomized controlled trial.

Detailed Description
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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 Sodium glucose co-transporter 2 inhibitor (SGLT2i) empagliflozin as an add-on therapy to insulin for overweight/obese adult patients with CFRD. We hypothesize that empagliflozin will be safe, well tolerated and will improve glycemic control in overweight/obese adult patients with CFRD. Specific Aim 1: Collect pilot data on the safety, tolerability, and feasibility of empagliflozin therapy in overweight/obese patients with CFRD to support a future larger randomized controlled trial. Hypothesis 1: Empagliflozin will be safe and well tolerated, with no evidence for electrolyte abnormalities, metabolic acidosis, ketosis or increased risk of severe hypoglycemia in overweight/obese adults people with CFRD. Specific Aim 2: Collect preliminary data to evaluate the effect of empagliflozin on glycemic outcomes. Hypothesis 2: Treatment with empagliflozin will improve glycemic control as indicated by glucose levels as measured by oral glucose tolerance test (OGTT), and on glycemic outcomes as measured by continuous glucose monitoring (CGM).

Official Title
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Empagliflozin in CFRD: Efficacy and Safety of SGLT2 Inhibitor Therapy in Overweight and Obese Subjects With Cystic Fibrosis-related Diabetes: a Pilot Study

Conditions
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Cystic Fibrosis-related Diabetes, Cystic Fibrosis

Intervention / Treatment
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* Drug: Empagliflozin
* Other: Placebo Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult subjects 18 years or older with CFRD and on insulin treatment BMI >25 kg/m2 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. Tubal ligation; 3. Use combination of two forms of contraception during the study including, oral, injectable, or implanted hormonal contraceptives, intrauterine device or barrier method. Exclusion Criteria: acute pulmonary exacerbation requiring IV antibiotics or systemic glucocorticoids within 4 weeks prior to baseline study procedures less than 12 weeks since start of a new CFTR corrector/modulator therapy type 1 diabetes Positive GAD 65 antibody or low fasting C-peptide (below the normal reference range of the lab) A history of diabetic ketoacidosis history of recurrent genital or urinary tract infections pregnancy or lactation prior solid organ transplant Chronic liver disease (based on problem list in medical records or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 times elevated above the upper limit of normal. chronic kidney disease (eGFR < 60mL/min/1.73 m2) Hypersensitivity to empagliflozin or any excipients of Jardiance History of eating disorder Non-English speakers and those unable to read in English • Diminished capacity to consent (study staff will utilize the MacCAT-CR for assessment)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This will be a placebo-controlled, randomized, double blind, crossover study with a 4 week wash out period. Collect pilot data on the safety, tolerability, and feasibility of empagliflozin therapy in overweight/obese patients with CFRD to support a future larger randomized controlled trial.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: empagliflozin<br>randomized to study medication (empagliflozin) 10 mg taken by mouth daily for 4 weeks | Drug: Empagliflozin<br>* Sodium glucose co-transporter 2 inhibitor<br>* Other names: SGLT2 inhibitor;|
| Placebo Comparator: placebo control<br>randomized to placebo control taken by mouth daily for 4 weeks | Other: Placebo Control<br>* Placebo Control<br>|

What is the study measuring?
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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
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Keywords Provided by Centre Hospitalier Valida
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CFRD, cystic fibrosis, cystic fibrosis related diabetes, empagliflozin