ADJUnct Semaglutide Treatment in Type 1 Diabetes

Obesity Clinical Trial

— 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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05537233
• Other study ID #: 22388
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 11, 2023
• Est. completion date: August 15, 2024

Study information

• Verified date: April 2024
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 115
• Est. completion date: August 15, 2024
• Est. primary completion date: August 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

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

1. Age >18 years at screening

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. Point-of-care 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 (exclusion only if doing MRI and CT scan)

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Obesity
• Type 1 Diabetes

Intervention

Drug:
• Semaglutide
Semaglutide up to 1 mg per week in addition to standard closed-loop therapy
• Placebo
Injection placebo up to 1 mg per week in addition to standard closed-loop therapy

Locations

Country	Name	City	State
United States	Barbara Davis Center for Diabetes	Aurora	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	Harold Schnitzer Diabetes Health Center	Portland	Oregon
United States	Iowa Diabetes Research Center	West Des Moines	Iowa

Sponsors (2)

Lead Sponsor	Collaborator
Viral N. Shah	Juvenile Diabetes Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in cardiac and aortic structure and function measured by cardiac magnetic resonance (CMR)	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.	26 weeks
Other	Change in ectopic fat volumes in the abdomen and around the heart	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.	26 weeks
Other	Changes in liver stiffness and hepatic steatosis	Changes in liver stiffness and hepatic steatosis measured by MRE and PDFF	26 weeks
Primary	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.	26 weeks
Secondary	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.	26 weeks
Secondary	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.	26 weeks
Secondary	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.	26 weeks
Secondary	Percent time spent in CGM-measured glucose >180 mg/dL	Percent of time spent in glucose range >180 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.	26 weeks
Secondary	Percent time spent in CGM-measured glucose >250mg/dL	Percent of time spent in glucose range >250 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.	26 weeks
Secondary	Percent time spent in CGM-measured glucose <70mg/dL	Percent of time spent in glucose range <70 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.	26 weeks
Secondary	Percent time spent in CGM-measured glucose <54 mg/dL	Percent of time spent in glucose range <54 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.	26 weeks
Secondary	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.	26 weeks
Secondary	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.	26 weeks
Secondary	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	26 weeks
Secondary	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	26 weeks
Secondary	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.	26 weeks
Secondary	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.	26 weeks
Secondary	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.	26 weeks
Secondary	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.	26 weeks
Secondary	Change in modifiable HCL settings	Example, basal-rate, insulin to carb ratio and correction factors for Tandem control-IQ, insulin to carb ratio and active insulin time for Medtronic 670 G/770G and target glucose level, insulin to carb ratio, correction factor and active insulin time for Omnipod 5.	26 weeks
Secondary	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.	26 weeks
Secondary	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.	26 weeks
Secondary	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.	26 weeks
Secondary	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.	26 weeks
Secondary	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.	26 weeks
Secondary	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.	26 weeks
Secondary	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.	26 weeks