Effect of Subcutaneous Semaglutide on Kidney Transplant Candidacy

NCT ID: NCT04741074

Last Updated: 2024-02-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-23
• Study Completion Date: 2023-01-31

Brief Summary

This randomized study evaluates the effect of subcutaneous semaglutide /in combination with lifestyle counseling in patients with type 2 diabetes mellitus (T2DM), overweight/obesity, and stage 4-5 chronic kidney disease (CKD) or dialysis-dependent end-stage kidney disease (ESKD) on patients' eligibility for kidney transplantation at the end of 9 months.

Detailed Description

Transplant policies regarding listing consider uncontrolled diabetes and severe obesity to be contraindications though there is great variability for exact BMI (35-45 kg/m2) and A1c (9-10%) thresholds for listing by center. Glucagon-lowering peptide-1 receptor agonists (GLP-1 RAs) offer great promise in this population as they have been shown to reduce weight, central adiposity, A1c, and risk of cardiovascular outcomes with similar effects in patients with and without CKD.

In this double-blind, placebo-controlled randomized controlled trial, the investigators will evaluate the effect of subcutaneous semaglutide 1.34 mg/ml (up to 1.0 mg per week) in combination with lifestyle counseling in patients with T2DM, overweight/obesity, and stage 4-5 CKD or dialysis-dependent ESKD on patients' eligibility for kidney transplantation in terms of diabetes control (A1c <9%) and obesity (BMI <35 kg/m2 or 35-40 kg/m2 with waist circumference <120 cm) at the end of 9 months.

Conditions

CKD; Diabetic Kidney Disease; Type 2 Diabetes Mellitus in Obese; Obesity; Severe Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Semaglutide

This arm will receive semaglutide.

Group Type: ACTIVE_COMPARATOR

Semaglutide 2 mg/1.5 ml (1.34 mg/ml), prefilled pen-injector for subcutaneous injection solution

Intervention Type: DRUG

Dose will be started at 0.25 mg per week. Dose escalation will occur every 4 weeks to mitigate risk of gastrointestinal side effects to a maximum dose of 1.0 mg per week.

Placebo

This arm will receive placebo.

Group Type: PLACEBO_COMPARATOR

Placebo 1.5 ml, prefilled pen-injector for subcutaneous injection solution

Intervention Type: DRUG

Matched placebo solution for injection will be provided by Novo Nordisk in a 1.5 ml pre-filled pen-injector for subcutaneous injection with the same instructions on dose escalation.

Interventions

Semaglutide 2 mg/1.5 ml (1.34 mg/ml), prefilled pen-injector for subcutaneous injection solution

Dose will be started at 0.25 mg per week. Dose escalation will occur every 4 weeks to mitigate risk of gastrointestinal side effects to a maximum dose of 1.0 mg per week.

Intervention Type: DRUG

Placebo 1.5 ml, prefilled pen-injector for subcutaneous injection solution

Matched placebo solution for injection will be provided by Novo Nordisk in a 1.5 ml pre-filled pen-injector for subcutaneous injection with the same instructions on dose escalation.

Intervention Type: DRUG

Other Intervention Names

semaglutide; placebo

Eligibility Criteria

Inclusion Criteria

1. - Age ≥ 18 years

2. - BMI 25-45 kg/m2

3. - T2DM

4. - Advanced CKD* (last eGFR <30 ml/min/1.73m2 in EHR or ESKD on dialysis prior to screening) or stage G3B/A2-3 CKD (eGFR 30 to <45 ml/min/1.73m2 with albumin/creatinine ratio >30 mg/g).

Exclusion Criteria

6. - Ability to provide informed consent before any trial-related activities

7. - Access to a telephone

• The cause of the CKD does not need to be due specifically to diabetes

1. - Active malignancy

2. - History of pancreatitis

3. - Active substance abuse

4. - Severe COPD

5. - Pulmonary fibrosis

6. - Symptomatic angina or recent myocardial infarction within 6 months

7. - Severe peripheral vascular disease

8. - Cirrhosis

9. - New York Health Association (NYHA) Class III-IV congestive heart failure

10. - Severe cognitive impairment

11. - Drug addiction

12. - History of non-adherence to therapy

13. - Active infection

14. - Expected life expectancy < 5 years

15. - Type 1 diabetes mellitus

16. - History of diabetic ketoacidosis within the last 12 months

17. - Planning on undergoing bariatric surgery in next 9 months.

18. - Pregnant, breast-feeding, or planned pregnancy prior to the end of participation or not using adequate contraceptive measures

19. - Self-reported average consumption of > 21 alcoholic beverages per week or binge drinking

20. - Psychiatric hospitalization in past year

21. - Principal investigator discretion (i.e. concerns about safety, compliance)

22. - Known or suspected allergy to trial medication

23. - Previous participation (i.e. randomized) in this trial

24. - Use of GLP1-RA or pramlintide within 90 days prior to screening

25. - Use of metformin (contraindicated with eGFR < 30 ml/min/1.73m2)

26. - Use of DPP-4 inhibitors within 30 days prior to screening

27. - Personal or family history of medullary thyroid cancer, multiple endocrine neoplasia types 2A and 2B syndrome

28. - Last hemoglobin A1c ≥ 12% or A1c <6% (to avoid risk of hypoglycemia) prior to screening

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Geisinger Clinic

OTHER

Sponsor Role: lead

Responsible Party

Alexander Chang

Assistant Professor, Clinical Research

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alex R Chang, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Geisinger Clinic

Locations

Geisinger Medical Center

Danville, Pennsylvania, United States

Geisinger Wyoming Valley

Wilkes-Barre, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Universal Trial Number

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-1050

Identifier Type: -

Identifier Source: org_study_id