Semaglutide vs Sitagliptin

NCT ID: NCT05195944

Last Updated: 2022-11-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-26
• Study Completion Date: 2024-12-31

Brief Summary

The effect of once daily dosing of oral Semaglutide versus once daily dosing Sitagliptin on glycemic control, body weight, and safety and tolerability will be compared in Liver Transplant Recipients with poorly-controlled Diabetes Mellitus.

Detailed Description

This will be a Phase IV, randomized, parallel, active-controlled, double-blind clinical trial, with one group receiving oral Semaglutide and the other group receiving oral sitagliptin, while continuing any background glucose-lowering medications such as metformin or insulin. Treatment duration will be 26 weeks. Sitagliptin has been chosen as comparator since it is an established oral antidiabetic drug (OAD) within the DPP-4i drug class. There will be a screening period, treatment period, and follow-up period. Furthermore, the investigators will collect biological samples and correlates including serum, plasma, and Intestinal Microbiome samples prior to initiation of study treatment and at the completion of the trial. The investigators will also perform Transient Elastography at these same visits to evaluate change in degree of participant graft steatosis.

Conditions

Liver Transplant; Complications; Diabetes Mellitus; NASH - Nonalcoholic Steatohepatitis; NAFLD

Study Design

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

Study Groups

Semaglutide

In the Semaglutide Arm, participants will receive daily: 1 tablet of Semaglutide and 1 tablet of Sitagliptin placebo for 26 weeks. The dosages of Semaglutide are 3 mg, 7 mg, and 14 mg.

Group Type: EXPERIMENTAL

Semaglutide Treatment

Intervention Type: DRUG

The participants will be provided with Semaglutide, titrated up to 14 mg. The starting dose of Semaglutide is 3 mg once daily. At week 4, the dose will be increased to 7 mg once daily. At week 8, the dose will be increased to 14 mg once daily and will be maintained at 14mg until End of Treatment (week 26). Throughout the 26 week treatment period, participants in this arm will also take one "sitagliptin placebo" tablet per day.

Sitagliptin

In the Sitagliptin arm, participants will receive daily: 1 tablet of 100 mg Sitagliptin and 1 tablet of Semaglutide placebo for 26 weeks.

Group Type: ACTIVE_COMPARATOR

Sitagliptin 100mg

Intervention Type: DRUG

participants will take 100mg tablet of Sitagliptin once daily, along with a "semaglutide placebo" pill for the duration of the 26 week treatment period

Interventions

Semaglutide Treatment

The participants will be provided with Semaglutide, titrated up to 14 mg. The starting dose of Semaglutide is 3 mg once daily. At week 4, the dose will be increased to 7 mg once daily. At week 8, the dose will be increased to 14 mg once daily and will be maintained at 14mg until End of Treatment (week 26). Throughout the 26 week treatment period, participants in this arm will also take one "sitagliptin placebo" tablet per day.

Intervention Type: DRUG

Sitagliptin 100mg

participants will take 100mg tablet of Sitagliptin once daily, along with a "semaglutide placebo" pill for the duration of the 26 week treatment period

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female, age ≥18 years at the time of signing informed consent.
• Willing and able to provide informed consent.
• Recipient of liver graft (Liver/Kidney recipients and retransplants allowed)
• Time from transplant surgery ≥ 3 months at time of screening visit with no evidence of active rejection. Liver enzymes must be stable with elevations no greater than 2xULN. However, if patients have elevated liver enzymes beyond 2xULN due to NASH, as confirmed on liver biopsy, they may be included.
• Patient diagnosed with type 2 diabetes or post-transplant diabetes
• Patients transplanted for hepatocellular carcinoma may be included provide their latest surveillance imaging is negative for recurrence
• The use of any immunosuppression regimen (calcineurin inhibitors, mycophenolate mofetil, maintenance prednisone or sirolimus) is acceptable
• HbA1c 7.0-10.5% (53-91 mmol/mol) (both inclusive, not under optimal glycemic control).

• Known history of proliferative retinopathy or maculopathy requiring acute treatment, unless stable
• History or presence of actively treated malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer, hepatocellular carcinoma, and carcinoma in situ.)

Exclusion Criteria

• Known or suspected hypersensitivity to trial products or related products.
• Previous participation in this trial.
• Active graft dysfunction that requires investigation (at screening).
• Currently receiving steroids (prednisone) for treatment of acute cellular rejection.
• Patients transplanted for multisystem genetic disorders such as amyloidosis or cystic fibrosis.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using highly-effective contraceptive methods ().
• Receipt of any investigational medicinal product within 90 days before screening.
• Any disorder or medical condition which, in the investigator's opinion, might jeopardize patient's safety or compliance with the protocol.
• Family or personal history of Multiple Endocrine Neoplasia Type 2 (MEN 2) or Medullary Thyroid Carcinoma (MTC).
• History of pancreatitis (acute or chronic).
• History of major surgical procedures involving the stomach and potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery).
• Any of the following: myocardial infarction (MI), stroke or hospitalization for unstable angina or transient ischemic attack within the past 180 days prior to the day of screening and randomization.
• Classified as being in New York Heart Association (NYHA) Class IV.
• Planned coronary, carotid or peripheral artery revascularization known on the day of screening.
• Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) <30 mL/min/1.73 m2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI).

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

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mamatha Bhat, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

Toronto General Hospital

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

U1111-1268-1934

Identifier Type: REGISTRY

Identifier Source: secondary_id

21-5640

Identifier Type: -

Identifier Source: org_study_id