Semaglutide in Adults With Type 1 Diabetes

Sponsor

University of Colorado, Denver (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05537233

Collaborator

Juvenile Diabetes Research Foundation (Other)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes Obesity	Drug: Semaglutide Drug: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Efficacy and Safety of Once Weekly Semaglutide in Adults With Obesity and Inadequately Controlled Type 1 Diabetes Using Hybrid Closed-Loop System.

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Nov 30, 2024

Anticipated Study Completion Date :

Oct 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Semaglutide Participants in this group will receive semaglutide once weekly injection in addition to their standard therapy	Drug: Semaglutide Semaglutide up to 1 mg per week in addition to standard insulin therapy
Placebo Comparator: Control Participants in this group will receive placebo once weekly injection in addition to their standard therapy	Drug: Placebo Injection placebo up to 1 mg per week in addition to standard insulin therapy

Arm

Intervention/Treatment

Experimental: Semaglutide

Participants in this group will receive semaglutide once weekly injection in addition to their standard therapy

Drug: Semaglutide

Semaglutide up to 1 mg per week in addition to standard insulin therapy

Placebo Comparator: Control

Participants in this group will receive placebo once weekly injection in addition to their standard therapy

Drug: Placebo

Injection placebo up to 1 mg per week in addition to standard insulin therapy

Outcome Measures

Primary Outcome Measures

Proportion of adults with T1D achieving composite outcome (CGM-measured time in range (TIR)>70% with time below range (TBR) of <5% and reduction in body weight by 5%) at 26 weeks in the semaglutide group compared to placebo group [26 weeks]
The primary endpoint (differences in proportion of patients achieving composite outcomes) will be compared, including the proportion of study participants achieving a reduction in body weight of 5% or more between 4 and 26 weeks and achieving TIR >70% and TBR of <5% at 26 weeks. This comparison between the proportion meeting the composite endpoint will be examined while adjusting for pre-specified covariates, baseline A1c and BMI. Baseline A1c is known to affect TIR (better improvement in TIR in those with higher A1c). Similarly, higher BMI may affect weight loss. Therefore, the investigator decided to use these covariates for adjustment. Sustain 7 post hoc analysis suggested that efficacy of semaglutide on glycemic control and weight loss remains the same regardless of baseline age, diabetes duration or sex. Therefore, the investigator did not include those variables in the pre-specified adjustment.

Secondary Outcome Measures

Change in HbA1c [26 weeks]
HbA1c will be measured at a central laboratory and change in Hba1c from 4 weeks to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.
Change in mean glucose [26 weeks]
Mean glucose (mg/dL) will be obtained by CGM and change in mean CGM glucose from 4 weeks to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.weeks will be compared by randomization group using intention to treat (ITT) analysis.
Percent time spent in CGM-measured glucose range of 70-140 mg/dL (time in tight target range; TTIR) [26 weeks]
Percent of time spent in tight glucose range (70-140 mg/dL) will be obtained by CGM and change in percent time in range from 4 weeks to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.
Percent time spent in CGM-measured glucose >180 mg/dL and >250 mg/dL [26 weeks]
Percent of time spent in glucose range (70-140 mg/dL) will be obtained by CGM and change in mean CGM glucose from 4 weeks to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.
Change in CGM measured glycemic variability (coefficient of variation) [26 weeks]
Glucose coefficient of variation (mg/dL) will be obtained by CGM and change in glucose CV from 4 weeks to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.
Differences in CGM metrics (mean glucose, TIR, TAR, TBR and CV) by daytime vs nighttime [26 weeks]
CGM metrics (TIR, TBR, TAR) during the day (6am - midnight) compared to at night (>midnight to <6am) will be compared by randomization group using an ITT analysis.
Percentage of patients achieving HbA1c <7% [26 weeks]
The proportion of patients achieving HbA1c <7% at 26 weeks will be compared by randomization group using an ITT analysis
Percentage of patients achieving TIR >70% [26 weeks]
The proportion of patients achieving TIR >70% at 26 weeks will be compared by randomization group using an ITT analysis
Change in patient reported quality of life [26 weeks]
Patient reported quality of life will be measured using a validated instrument (ADDQOL) and the change in score from 4 to 26 weeks will be compared by randomization group using an ITT analysis.
Change in insulin dose (total daily dose, units/kg of body weight) [26 weeks]
The change in total daily dose of insulin per kg of body weight from 4 to 26 weeks will be compared by randomization group using an ITT analysis.
Change in weight [26 weeks]
The change in kg of body weight from 4 to 26 weeks will be compared by randomization group using an ITT analysis.
Severe hypoglycemia and diabetic ketoacidosis episodes [26 weeks]
The number of severe hypoglyemia and diabetic ketoacidosis events during the study period will be compared by randomization group using an ITT analysis.
Change in blood pressure (systolic, diastolic, mean and pulse pressure) [26 weeks]
The change in blood metric metrics (systolic, diastolic, mean arterial pressure and pulse pressure) from 4 weeks to 26 weeks will be compared by randomization group using an ITT analysis.
Change in brachial arterial distensibility (Brach D), augmentation index by radial artery tonometry [pulse wave analysis [PWA]), pulse wave velocity (PWV)], and carotid atherosclerosis by carotid intima media thickness (cIMT) [26 weeks]
Changes in arterial stiffness measures (BrachD, PWV, PWA) and carotid IMT from 4 weeks to 26 weeks will be compared by randomization group using an ITT analysis.
Change in lipid parameters [26 weeks]
Changes in fasting lipids (total cholesterol, triglyceride, LDL-C and HDL-C) from 4 to 26 weeks will be compared by randomization group using an ITT analysis.
Change in albumin to creatinine ratio (ACR) [26 weeks]
Changes in renal function as measured by urinary ACR from 4 to 26 weeks will be compared by randomization group using an ITT analysis.
Change in BMI (Kg/m2) [26 weeks]
Change in body mass index (BMI) calculated as kg body weight per meter squared of height from 4 to 26 weeks will be compared by randomization group using an ITT analysis.
Change in estimated glomerular filtration rate (eGFR) [26 weeks]
Changes in renal function as measured by eGFR from 4 to 26 weeks will be compared by randomization group using an ITT analysis.

Other Outcome Measures

Change in cardiac and aortic structure and function measured by cardiac magnetic resonance (CMR) [26 weeks]
Changes in cardiac and aortic structure and function measured by cardiac magnetic resonance imaging from 4 to 26 weeks will be compared by randomization group using an ITT analysis.
Change in ectopic fat volumes in the abdomen and around the heart [26 weeks]
Changes in fat volume around the heart and in the abdomen from 4 to 26 weeks will be compared by randomization group using an ITT analysis.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Age >18 years at screening
Patients with clinical diagnosis of T1D diagnosed for at least 12 months
Patient is on FDA- approved hybrid closed-loop system (HCL) for ≥ 3 months
Willing to use once weekly semaglutide
Point-of-care HbA1c >7.0% and <10.0%
Body mass index ≥30 kg/m2
Ability to provide informed consent before any trial-related activities

Exclusion Criteria:

Age ≤18 years and ≤60 years
HbA1c ≤7.0 % or ≥ 10.0% at screening
Less than 12 months of insulin treatment
Use of unapproved insulin for HCL system. E.g. use of Fiasp in the Tandem Control-IQ system
Unavailability of compatible smart phone for device data transfer
Current use of multiple daily injection or inhaled insulin (Afrezza)
Patients with T1D using any glucose lowering medications other than insulin at the time of screening
Pregnancy, breast feeding, and positive pregnancy test during screening
Women of childbearing age wanting to become pregnant or not using adequate contraceptive measures
Current use (≥ 2 weeks of continuous use) of any steroidal medication, or anticipated long-term steroidal treatment (>4 weeks continuously), during the study period
Use of GLP-1RA or weight loss medications in the past 3 month
Clinical diagnosis/history of gastroparesis or gastric motility disorders
Fasting serum triglycerides >500 mg/dL
Planning for bariatric surgery during the study period
eGFR below 45 ml/min/1.73 m^2 using MDRD formula
History of severe hypoglycemia in the previous 3 months
History of diabetic ketoacidosis requiring hospitalization in the past 3 months
History of allergy to any form of insulin, GLP-1RA or its excipients
History of any form of pancreatitis
History of stroke, myocardial infarction in the past 3 months
History of congestive heart failure class III or IV
History of acute or chronic liver disease
History of malignancy requiring chemotherapy, surgery or radiation in previous 5 years
Personal or family history of multiple endocrine neoplasia type 2 (MEN-2) or familial thyroid carcinoma or non-familial medullary thyroid carcinoma
Use of investigational drugs within 5 half-lives prior to screening
Participation to other intervention trials during the study period
Any comorbidities or medical conditions such as severe psychiatric disorder that make a person unfit for the study at the discretion of the investigators

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barbara Davis Center for Diabetes	Aurora	Colorado	United States	80045
2	Iowa Diabetes Research Center	West Des Moines	Iowa	United States	50265
3	Henry Ford Hospital	Detroit	Michigan	United States	48202
4	Harold Schnitzer Diabetes Health Center	Portland	Oregon	United States	97239