Clinical trial NCT05537233: ADJUnct Semaglutide Treatment in Type 1 Diabetes
Official title: Efficacy and Safety of Once Weekly Semaglutide in Adults With Obesity and Inadequately Controlled Type 1 Diabetes Using Hybrid Closed-Loop System.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 1 Diabetes
Obesity
Keywords: Type 1 diabetes
Obesity
HbA1c
Time-in-range
Weight loss
Cardiovascular risk
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: Juvenile Diabetes Research Foundation
First posted: 2022-09-13
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the use of once weekly semaglutide injection in inadequately controlled obese adults with type 1 diabetes (T1D) using FDA-approved hybrid closed-loop therapies.

Detailed description: After being informed about the study and potential risks, all patients given written informed consent will undergo a 2-week screening period to determine eligibility for study entry. At week 0, patients who meet the eligibility requirements will be randomized in a double-blind manner using computer generated randomization scheme to receive either semaglutide or placebo (1:1 ratio) for 26 weeks.

Eligibility criteria: Inclusion Criteria:

For an eligible subject, all inclusion criteria must be answered "yes"

1. Age ≥18 and ≤ 65 years
2. Patients with clinical diagnosis of T1D diagnosed for at least 12 months
3. Patient is on FDA- approved hybrid closed-loop system for ≥ 3 months
4. Willing to use once weekly semaglutide
5. Willing to share devices (HCL system) data uploads
6. HbA1c \>7.0% and \<10.0%
7. Body mass index ≥30 kg/m2
8. Has current glucagon product to treat severe hypoglycemia
9. Has current ketone meters to check ketones
10. Ability to provide informed consent before any trial-related activities

Exclusion Criteria:

1. Age \<18 years and \>65 years
2. HbA1c ≤7.0 % or ≥ 10.0% at screening
3. Less than 12 months of insulin treatment
4. Use of unapproved insulin for HCL system. E.g. use of Fiasp in the Tandem Control-IQ system
5. Not willing to share the devices (HCL system) data uploads
6. Non compatible devices (e.g. pump, CGM or smart phones) for data transfer
7. Current use of multiple daily injection or inhaled insulin (Afrezza)
8. Patients with T1D using any glucose lowering medications other than insulin at the time of screening
9. Pregnancy, breast feeding, and positive pregnancy test during screening
10. Women of childbearing age wanting to become pregnant
11. Unwilling to use acceptable contraceptive methods (for both men and women) during the trial period
12. Current use (≥ 2 weeks of continuous use) of any steroidal medication, or anticipated long-term steroidal treatment (\>4 weeks continuously), during the study period
13. Use of GLP-1RA or weight loss medications in the past 3 month
14. Clinical diagnosis/history of gastroparesis or gastric motility disorders
15. Serum triglycerides \>500 mg/dL
16. Planning for bariatric surgery during the study period
17. eGFR below 45 ml/min/1.73 m\^2 using CKD-EPI formula
18. History of severe hypoglycemia in the previous 3 months
19. History of diabetic ketoacidosis requiring hospitalization in the past 3 months
20. History of allergy to any form of insulin, GLP-1RA or its excipients
21. History of any form of pancreatitis
22. History of stroke, myocardial infarction in the past 3 months
23. History of congestive heart failure class III or IV
24. History of acute or chronic liver disease
25. History of malignancy requiring chemotherapy, surgery or radiation in previous 5 years
26. Personal or family history of multiple endocrine neoplasia type 2 (MEN-2) or familial thyroid carcinoma or non-familial medullary thyroid carcinoma
27. Have a pacemaker, metal implants, or aneurysm clips or weigh \>330 lbs (exclusion only if doing MRI)
28. Use of investigational drugs within 5 half-lives prior to screening
29. Participation to other intervention trials during the study period
30. Any comorbidities or medical conditions such as severe psychiatric disorder that make a person unfit for the study at the discretion of the investigators

Primary outcomes:
measure: Proportion of adults with T1D achieving composite outcome (CGM-measured time in range (TIR)>70% with time below range (TBR) of <4% and reduction in body weight by 5%) at 26 weeks in the semaglutide group compared to placebo group
timeFrame: 26 weeks
Secondary outcomes:
measure: Change in HbA1c
timeFrame: 26 weeks
measure: Change in mean glucose
timeFrame: 26 weeks
measure: Percent time spent in CGM-measured glucose range of 70-140 mg/dL (time in tight target range; TTIR)
timeFrame: 26 weeks
measure: Percent time spent in CGM-measured glucose >180 mg/dL
timeFrame: 26 weeks
measure: Percent time spent in CGM-measured glucose >250mg/dL
timeFrame: 26 weeks
measure: Percent time spent in CGM-measured glucose <70mg/dL
timeFrame: 26 weeks
measure: Change in CGM measured glycemic variability (coefficient of variation)
timeFrame: 26 weeks
measure: Change in patient reported quality of life
timeFrame: 26 weeks
measure: Change in weight
timeFrame: 26 weeks
measure: Change in BMI (Kg/m2)
timeFrame: 26 weeks
measure: Severe Hypoglycemia and diabetic ketoacidosis events
timeFrame: 26 weeks
Other outcomes:
measure: Proportion of participants with HbA1c <7%
timeFrame: 26 weeks
measure: Proportion of participants with HbA1c <7.5%
timeFrame: 26 weeks
measure: HbA1c improvement
timeFrame: 26 weeks
measure: HbA1c improvement of >0.4% from baseline
timeFrame: 26 weeks
measure: Proportion of participants achieving TIR >70%
timeFrame: 26 weeks
measure: Proportion of participants achieving TITR >50%
timeFrame: 26 weeks
measure: Proportion of participants achieving TIR >80%
timeFrame: 26 weeks
measure: Proportion of participants achieving TITR >60%
timeFrame: 26 weeks
measure: Number of TBR<70 events
timeFrame: 26 weeks
measure: Number of TBR <54 events
timeFrame: 26 weeks
measure: Change in total daily dose of insulin (TDD, Units per day and U/Kg/Day)
timeFrame: 26 weeks
measure: Proportion achieving weight loss ≥5%
timeFrame: 26 weeks
measure: Proportion achieving weight loss ≥10%
timeFrame: 26 weeks
measure: Proportion of achieving BMI <30 kg/m2
timeFrame: 26 weeks
measure: Proportion of achieving BMI <25 kg/m2
timeFrame: 26 weeks
measure: Change in systolic blood pressure (SBP)
timeFrame: 26 weeks
measure: Change in diastolic blood pressure (DBP)
timeFrame: 26 weeks
measure: Change in pulse pressure
timeFrame: 26 weeks
measure: Change in triglyceride/HDL ratio
timeFrame: 26 weeks
measure: Change in Brach D
timeFrame: 26 weeks
measure: Change in carotid intima media thickness (cIMT)
timeFrame: 26 weeks
measure: Change in femoral to carotid pulse wave velocity (m/s)
timeFrame: 26 weeks
measure: Change in urine albumin to creatinine ratio (ACR)
timeFrame: 26 weeks
measure: Quality of life (Diabetes Dependent QOL)
timeFrame: 26 weeks
measure: Change in CGM metrics by daytime vs nighttime
timeFrame: 26 weeks
measure: AID setting adjustment
timeFrame: 26 weeks
measure: Change in basal insulin per day
timeFrame: 26 weeks
measure: Change in total boluses per day
timeFrame: 26 weeks
measure: Achievement of primary outcome and key secondary outcomes by types of AID systems
timeFrame: 26 weeks
measure: Change in Carbohydrate intake per day (grams/day)
timeFrame: 26 weeks
measure: Change in total bolus insulin per day
timeFrame: 26 weeks
measure: Change in eGFR
timeFrame: 26 weeks
measure: Change in Fib-4 score
timeFrame: 26 weeks
measure: Change in HSI (hepatic steatosis index)
timeFrame: 26 weeks
measure: Change in MRI measured pulse wave velocity and longitudinal strain
timeFrame: 26 weeks
measure: Change in LDL-C
timeFrame: 26 weeks
measure: Change in TC
timeFrame: 26 weeks
measure: Change in TG
timeFrame: 26 weeks
measure: Change in HDL-C
timeFrame: 26 weeks
measure: Proportion with ACR <30 at 26 weeks
timeFrame: 26 weeks
measure: Proportion with change in ACR from >30 to <30
timeFrame: 26 weeks
measure: Achievement of primary outcomes by baseline BMI (BMI <35 vs >35)
timeFrame: 26 weeks
measure: Achievement of primary outcomes by baseline A1c (A1c <7.5% vs >7.5%)
timeFrame: 26 weeks
Locations:
city: Aurora
country: United States
facility: Barbara Davis Center for Diabetes
state: Colorado
city: West Des Moines
country: United States
facility: Iowa Diabetes Research Center
state: Iowa
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Portland
country: United States
facility: Harold Schnitzer Diabetes Health Center
state: Oregon
Study officials:
affiliation: Indiana University
name: Viral N Shah, MD
role: PRINCIPAL_INVESTIGATOR
References: