Clinical trial NCT04741074: Effect of Subcutaneous Semaglutide on Kidney Transplant Candidacy
Official title: A RAndomized trIal Examining the Effect of Subcutaneous Semaglutide on Kidney Transplant Candidacy for Patients With Stage 4-5 CKD or Dialysis-dependent ESKD
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: CKD
Diabetic Kidney Disease
Type 2 Diabetes Mellitus in Obese
Obesity
Severe Obesity
Keywords: ckd
obesity
kidney transplant
transplant wait list
diabetic kidney disease
glp-1
semaglutide
Lead sponsor: Geisinger Clinic
Sponsor class: OTHER
First posted: 2021-02-05
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).
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

Primary outcomes:
measure: Kidney Transplant Eligibility
timeFrame: Ascertained at the end of 9 months
Secondary outcomes:
measure: Change in Hemoglobin A1c (HgbA1c)
timeFrame: From baseline to 9 months
measure: Change in BMI
timeFrame: From baseline to 9 months
measure: Change in Waist Circumference
timeFrame: From baseline to 9 months
measure: Change in Waist-to-hip Ratio
timeFrame: From baseline to 9 months
measure: Change in Body Fat Percentage
timeFrame: From baseline to 9 months
measure: New Activation on the Transplant List
timeFrame: Assessed at end of 9 months
measure: Receipt of Kidney Transplant
timeFrame: Assessed at end of 9 months
Other outcomes:
measure: Change in Low-Density Lipoprotein (LDL)
timeFrame: Baseline to 9 months
measure: Change in Triglycerides
timeFrame: Baseline to 9 months
measure: Change in Systolic Blood Pressure
timeFrame: Baseline to 9 months
measure: Change in Diastolic Blood Pressure
timeFrame: Baseline to 9 months
measure: Change in Albuminuria Among Subset of Participants Without End-stage Kidney Disease
timeFrame: Baseline to 9 months
measure: Change in Estimated Glomerular Filtration (eGFR) Rate Among Subset of Participants Without End-stage Kidney Disease
timeFrame: Baseline to 9 months
measure: All-cause Hospitalizations
timeFrame: Entire 9-month study period
measure: Cardiovascular Disease (CVD) Events
timeFrame: Entire 9-month study period
measure: Proportion Experiencing Doubling of Creatinine or End-stage Kidney Disease
timeFrame: Entire 9-month study period
measure: Proportion Experiencing Death
timeFrame: Entire 9-month study period
measure: Proportion Experiencing Gastrointestinal Disorders
timeFrame: Entire 9-month study period
measure: Proportion Experiencing Gallbladder Disorders
timeFrame: Entire 9-month study period
measure: Proportion Experiencing Neoplasms
timeFrame: Entire 9-month study period
measure: Proportion Experiencing Hepatic Events
timeFrame: Entire 9-month study period
measure: Proportion Experiencing Allergic Reactions
timeFrame: Entire 9-month study period
measure: Proportion Experiencing Injection-site Reactions
timeFrame: Entire 9-month study period
measure: Proportion Experiencing Hypoglycemia Events
timeFrame: Entire 9-month study period
measure: Proportion Experiencing Acute Pancreatitis Events
timeFrame: Entire 9-month study period
Locations:
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Wyoming Valley
state: Pennsylvania
Study officials:
affiliation: Geisinger Clinic
name: Alex R Chang, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: