ADJUnct Semaglutide Treatment in Type 1 Diabetes (ADJUST-T1D)
Primary Purpose
Type 1 Diabetes, Obesity
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Semaglutide
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes focused on measuring Type 1 diabetes, Obesity, HbA1c, Time-in-range, Weight loss, Cardiovascular risk
Eligibility Criteria
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 for ≥ 3 months
- Willing to use once weekly semaglutide
- Willing to share devices (HCL system) data uploads
- Point-of-care HbA1c >7.0% and <10.0%
- Body mass index ≥30 kg/m2
- Has current glucagon product to treat severe hypoglycemia
- Has current ketone meters to check ketones
- 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
- Not willing to share the devices (HCL system) data uploads
- 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
- Have a pacemaker, metal implants, or aneurysm clips (exclusion only if doing MRI and CT scan)
- 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
Sites / Locations
- Barbara Davis Center for DiabetesRecruiting
- Iowa Diabetes Research CenterRecruiting
- Henry Ford HospitalRecruiting
- Harold Schnitzer Diabetes Health CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Semaglutide
Control
Arm Description
Participants in this group will receive semaglutide once weekly injection in addition to their standard closed-loop therapy
Participants in this group will receive placebo once weekly injection in addition to their standard closed-loop therapy
Outcomes
Primary Outcome Measures
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
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 <4% 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
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
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)
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
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)
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
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%
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%
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
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)
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
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
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)
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)
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
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)
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)
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)
Changes in renal function as measured by eGFR from 4 to 26 weeks will be compared by randomization group using an ITT analysis.
Change in NAFLD biomarkers
Changes in NAFLD biomarkers, HSI and FIB-4 from 4 to 26 weeks will be compared by randomization group using an ITT analysis.
Full Information
NCT ID
NCT05537233
First Posted
August 23, 2022
Last Updated
July 17, 2023
Sponsor
University of Colorado, Denver
Collaborators
Juvenile Diabetes Research Foundation
1. Study Identification
Unique Protocol Identification Number
NCT05537233
Brief Title
ADJUnct Semaglutide Treatment in Type 1 Diabetes
Acronym
ADJUST-T1D
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
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 11, 2023 (Actual)
Primary Completion Date
July 30, 2024 (Anticipated)
Study Completion Date
October 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
Juvenile Diabetes Research Foundation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes, Obesity
Keywords
Type 1 diabetes, Obesity, HbA1c, Time-in-range, Weight loss, Cardiovascular risk
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Semaglutide
Arm Type
Experimental
Arm Description
Participants in this group will receive semaglutide once weekly injection in addition to their standard closed-loop therapy
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Participants in this group will receive placebo once weekly injection in addition to their standard closed-loop therapy
Intervention Type
Drug
Intervention Name(s)
Semaglutide
Intervention Description
Semaglutide up to 1 mg per week in addition to standard closed-loop therapy
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Injection placebo up to 1 mg per week in addition to standard closed-loop therapy
Primary Outcome Measure Information:
Title
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
Description
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 <4% 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.
Time Frame
26 weeks
Secondary Outcome Measure Information:
Title
Change in HbA1c
Description
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.
Time Frame
26 weeks
Title
Change in mean glucose
Description
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.
Time Frame
26 weeks
Title
Percent time spent in CGM-measured glucose range of 70-140 mg/dL (time in tight target range; TTIR)
Description
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.
Time Frame
26 weeks
Title
Percent time spent in CGM-measured glucose >180 mg/dL and >250 mg/dL
Description
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.
Time Frame
26 weeks
Title
Change in CGM measured glycemic variability (coefficient of variation)
Description
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.
Time Frame
26 weeks
Title
Differences in CGM metrics (mean glucose, TIR, TAR, TBR and CV) by daytime vs nighttime
Description
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.
Time Frame
26 weeks
Title
Percentage of patients achieving HbA1c <7%
Description
The proportion of patients achieving HbA1c <7% at 26 weeks will be compared by randomization group using an ITT analysis
Time Frame
26 weeks
Title
Percentage of patients achieving TIR >70%
Description
The proportion of patients achieving TIR >70% at 26 weeks will be compared by randomization group using an ITT analysis
Time Frame
26 weeks
Title
Change in patient reported quality of life
Description
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.
Time Frame
26 weeks
Title
Change in insulin dose (total daily dose, units/kg of body weight)
Description
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.
Time Frame
26 weeks
Title
Change in weight
Description
The change in kg of body weight from 4 to 26 weeks will be compared by randomization group using an ITT analysis.
Time Frame
26 weeks
Title
Severe hypoglycemia and diabetic ketoacidosis episodes
Description
The number of severe hypoglyemia and diabetic ketoacidosis events during the study period will be compared by randomization group using an ITT analysis.
Time Frame
26 weeks
Title
Change in blood pressure (systolic, diastolic, mean and pulse pressure)
Description
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.
Time Frame
26 weeks
Title
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)
Description
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.
Time Frame
26 weeks
Title
Change in lipid parameters
Description
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.
Time Frame
26 weeks
Title
Change in albumin to creatinine ratio (ACR)
Description
Changes in renal function as measured by urinary ACR from 4 to 26 weeks will be compared by randomization group using an ITT analysis.
Time Frame
26 weeks
Title
Change in BMI (Kg/m2)
Description
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.
Time Frame
26 weeks
Title
Change in estimated glomerular filtration rate (eGFR)
Description
Changes in renal function as measured by eGFR from 4 to 26 weeks will be compared by randomization group using an ITT analysis.
Time Frame
26 weeks
Title
Change in NAFLD biomarkers
Description
Changes in NAFLD biomarkers, HSI and FIB-4 from 4 to 26 weeks will be compared by randomization group using an ITT analysis.
Time Frame
26 weeks
Other Pre-specified Outcome Measures:
Title
Change in cardiac and aortic structure and function measured by cardiac magnetic resonance (CMR)
Description
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.
Time Frame
26 weeks
Title
Change in ectopic fat volumes in the abdomen and around the heart
Description
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.
Time Frame
26 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 for ≥ 3 months
Willing to use once weekly semaglutide
Willing to share devices (HCL system) data uploads
Point-of-care HbA1c >7.0% and <10.0%
Body mass index ≥30 kg/m2
Has current glucagon product to treat severe hypoglycemia
Has current ketone meters to check ketones
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
Not willing to share the devices (HCL system) data uploads
Non compatible devices (e.g. pump, CGM or smart phones) for 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
Unwilling to use acceptable contraceptive methods (for both men and women) during the trial period
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 CKD-EPI 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
Have a pacemaker, metal implants, or aneurysm clips (exclusion only if doing MRI and CT scan)
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Henon Gebre, MPH
Phone
303-724-3884
Email
Henon.Gebre@cuanschutz.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Viral N Shah, MD
Organizational Affiliation
University of Colorado/Barbara Davis Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Barbara Davis Center for Diabetes
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Henon Gebre
Phone
303-724-3884
First Name & Middle Initial & Last Name & Degree
Viral N Shah, MD
Facility Name
Iowa Diabetes Research Center
City
West Des Moines
State/Province
Iowa
ZIP/Postal Code
50265
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tara Herrold
Phone
515-329-6800
First Name & Middle Initial & Last Name & Degree
Anuj Bharvaga, MD
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Davida Kruger, NP
Facility Name
Harold Schnitzer Diabetes Health Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Deboarh Branigan
First Name & Middle Initial & Last Name & Degree
Andrew Ahmann, MD
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD will be available once the study is completed.
IPD Sharing Time Frame
Study protocol is available
IPD Sharing Access Criteria
Anyone can access the protocol
Learn more about this trial
ADJUnct Semaglutide Treatment in Type 1 Diabetes
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