Effect of Weekly GLP1 Agonist Treatment in "Double Diabetes" (TOLEDDO)

• ClinicalTrials.gov Identifier: NCT05305794
• Recruitment Status: Active, not recruiting
• First Posted: March 31, 2022
• Last Update Posted: May 3, 2024
• Sponsor: Centre Hospitalier Universitaire Dijon
• Information provided by (Responsible Party): Centre Hospitalier Universitaire Dijon

Tracking Information

• First Submitted Date: March 9, 2022
• First Posted Date: March 31, 2022
• Last Update Posted Date: May 3, 2024
• Actual Study Start Date: July 12, 2022
• Estimated Primary Completion Date: August 2026 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 30, 2022): Percentage of time spent within glycemic target range (0.70-1.80 g/l) [ Time Frame: Change from baseline at Day 180 ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effect of Weekly GLP1 Agonist Treatment in "Double Diabetes"
• Official Title: Effect of Weekly GLP1 Agonist Treatment in "Double Diabetes": a Randomized Open-label Study

Brief Summary

Between 16% and 22% of type 1 diabetic patients present a clinical and biological profile of insulin resistance favored by a family history of type 2 diabetes or metabolic syndrome. They constitute a group of patients with "double diabetes" since they have both true type 1 diabetes and inherited insulin resistance, typical of type 2 diabetes.

For several years, GLP1 agonists have been successfully used in the treatment of type 2 diabetes, leading to very significant improvements in glycemic control and weight loss.

Because of the insulin-sensitizing power of GLP1 agonists, the investigators hypothesize that they could reduce insulin resistance in patients with "double diabetes" and thus improve their glycemic control.

The investigators propose to use in this study semaglutide, the most recent and most potent GLP1 agonist (superiority demonstrated compared to exenatide LP and dulaglutide) and administered as a weekly subcutaneous injection (in contrast to liraglutide administered daily).

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Double Diabetes

Intervention

• Drug: Insulin + semaglutide treatment
  Usual insulin treatment + semaglutide (0.25 mg/week for 4 weeks, then 0.50 mg/week for 4 weeks, then 1 mg/week for 18 weeks, i.e. a total duration of 26 weeks). Upon introduction of semaglutide (ozempic) treatment, insulin doses will be reduced by 10% (basal insulin, basal rate and bolus)
• Drug: Usual insulin treatment
  Usual insulin treatment
• Biological: Biological check-up
  at D0, D90 and D180

Study Arms

• Experimental: Semaglutide
  Interventions:

  • Drug: Insulin + semaglutide treatment
  • Biological: Biological check-up
• Active Comparator: Control
  Interventions:

  • Drug: Usual insulin treatment
  • Biological: Biological check-up

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: March 30, 2022): 76
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2026
• Estimated Primary Completion Date: August 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Person who has given written consent
• Patient over 18 years of age
• Patient with type 1 diabetes confirmed by a C-peptide below laboratory standards
• Age at diagnosis < 35 years
• Treated with optimized insulin therapy (multi-injections or pump) for at least 1 year, having received specific therapeutic education on insulin dose adaptation.
• BMI (weight/height2) ≥ 27 Kg/m².

• At least one of the following criteria:

  • Family history of type 2 diabetes (parents, grandparents, uncles, aunts, brothers and sisters)
  • Family history of obesity (BMI>30 Kg/m2) (parents, grandparents, uncles, aunts, siblings)
  • Triglycerides > 1.50g/l (1.7mmol/l)
  • HDL< 0.5 g/l (1.29 mmol/l) in women, HDL<0.4 g/l (1.03 mmol/l) in men
• HbA1c ≥ 7.5% and < 12% in the 3 months preceding inclusion
• Having continuous glucose monitoring by a CGM (Holter Glucose Monitoring) system: Guardian, Dexcom or Free Style Libre
• For women of childbearing age: using an effective method of contraception until 2 months after the end of treatment. Effective contraception includes: hormonal contraception, intrauterine device, bilateral tubal occlusion, vasectomy and sexual abstinence

Exclusion Criteria:

• person not affiliated to national health insurance
• Pregnant, parturient or breastfeeding woman
• HbA1c ≥12% in the 3 months preceding inclusion.
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy, confirmed by a fundus examination performed in the 6 months preceding the selection
• Person under a measure of legal protection (curatorship, guardianship)
• Renal insufficiency (GFR<30 ml/mn)
• Hepatic insufficiency (INR> 1.5)
• BMI >40 kg/m².
• History of bariatric surgery
• History of pancreatitis
• Allergy to the active substance or to one of the excipients of OZEMPIC®.
• Patients treated with GLP1 agonists or oral antidiabetics in the month preceding month prior to inclusion

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT05305794
• Other Study ID Numbers: BOUILLET PHRCI 2020
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Centre Hospitalier Universitaire Dijon
• Original Responsible Party: Same as current
• Current Study Sponsor: Centre Hospitalier Universitaire Dijon
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Centre Hospitalier Universitaire Dijon
• Verification Date: May 2024