Effect of Subcutaneous Semaglutide on Kidney Transplant Candidacy (RAISE-KT)

Geisinger Health

Status and phase: Terminated; Phase 3

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

Treatments: Drug: Placebo 1.5 ml, prefilled pen-injector for subcutaneous injection solution; Drug: Semaglutide 2 mg/1.5 ml (1.34 mg/ml), prefilled pen-injector for subcutaneous injection solution

Study type: Interventional

Funder types: Other

Identifiers

NCT04741074

2020-1050

Universal Trial Number (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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).
5. • Fulfill kidney transplant listing criteria except for one or more of the following reasons (1: uncontrolled diabetes [A1c ≥9%); 2: severe obesity (BMI ≥ 40 kg/m2 or BMI 35-40 kg/m2 with waist circumference >120 cm). See exclusion criteria for general contraindications used for transplant listing used by majority of U.S. transplant centers].
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

Exclusion Criteria (General contraindications used for transplant listing used by majority of U.S. transplant centers)

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

    Additional exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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15 participants in 2 patient groups, including a placebo group

Semaglutide

Active Comparator group

Description:

This arm will receive semaglutide.

Treatment:

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

Placebo

Placebo Comparator group

Description:

This arm will receive placebo.

Treatment:

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