Semaglutide vs Sitagliptin

NCT05195944 | Unknown Phase 4 DMC

• 2 other identifiers: 21-5640U1111-1268-1934
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Change in HbA1c level (%)

  Evaluate the change in glycemic control within and between study groups by measuring HbA1c

  Baseline to 26 weeks

Secondary Outcomes (2)

• Change in body weight (kg)

  baseline to 26 weeks

• Number of treatment-emergent adverse events

  26 weeks

Other Outcomes (2)

• Change in aspartate aminotransferase (AST) level

  baseline to 26 weeks

• Change in alanine aminotransferase (ALT) level

  baseline to 26 weeks

Study Arms (2)

Semaglutide

EXPERIMENTAL

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.

Drug: Semaglutide Treatment

Sitagliptin

ACTIVE COMPARATOR

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

Drug: Sitagliptin 100mg

Interventions

Semaglutide Treatment 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.

Semaglutide

Sitagliptin 100mg 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

Sitagliptin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus; Non-alcoholic Fatty Liver Disease

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• Mamatha Bhat, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2021
• First Posted: January 19, 2022
• Study Start: October 26, 2022
• Primary Completion: April 1, 2024
• Study Completion: December 1, 2024
• Last Updated: November 8, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)