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Randomized Double Blinded Placebo-Controlled w/Semaglutide to Prevent Weight Gain After Liver Transplant

Primary Purpose

NAFLD

Status

Not yet recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Semaglutide Pen Injector

Placebo

About this trial

This is an interventional prevention trial for NAFLD focused on measuring Liver Transplant

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female age 18-75 years who received LT for any indication (i.e. NASH, hepatitis C, alcohol-induced cirrhosis, autoimmune hepatitis, etc.)
Liver transplant surgery within 8-24 weeks prior to randomization
Presence of diabetes (HbA1c≥6.5% or use of diabetes medications) or pre-diabetes (HbA1c >5.7%)
Ability to provide informed consent
Discharged from the hospital following LT surgery
Tolerating diet
Normal graft function* (determined by treating hepatologist/surgeon based on clinical status and hepatic panel)
Stable immunosuppression according the VCU (Virginia Commonwealth University) post-LT protocols ** (i.e. calcineurin inhibitors + mycophenolate)
Eligible female patients will be (1) non-pregnant, evidenced by a negative urine pregnancy test, (2) non-lactating, (3)surgically sterile or post-menopausal, or they will agree to continue to use an accepted method of birth control during the study

Exclusion Criteria:

BMI≤ 27kg/m2
GFR (Glomerular Filtration Rate) ≤ 25 ml/min/1.73m2
Type 1 autoimmune diabetes (by anti-GAD (glutamic acid decarboxylase) or history of ketoacidosis)
History of gastroparesis
Familial or personal history of medullary thyroid cancer or MEN (Multiple Endocrine Neoplasia) 2
History of pancreatitis
History of active malignancy post- LT with the exception of non-melanoma skin cancers
History of uncontrolled or unstable diabetic retinopathy or maculopathy
Acute cellular rejection
Hepatic artery thrombosis
Medical non-compliance
Active treatment with GLP (glucagon-like peptide)-1RA (receptor agonist) or SGLT (sodium-glucose cotransporter)-2 inhibitors at time of screening
History of hypersensitivity to semaglutide or its excipients
Women who are nursing, pregnant, or planning to become pregnant during the study, or are not using adequate contraceptive measures

Sites / Locations

Virginia Commonwealth University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Semaglutide

Placebo

Arm Description

Semaglutide administered subcutaneously (under the skin) once weekly. There will be a 20 week lead in period of dose escalation before reaching the target dose of 2.4mg weekly. Semaglutide will then be administered at the maximum tolerated dose for 52 weeks.

Placebo administered subcutaneously (under the skin) once weekly.

Outcomes

Primary Outcome Measures

Change in weight

Weight measured in kilograms

Secondary Outcome Measures

Development of NAFLD

Number of participant who develop NAFLD by the end of treatment will be measured via MRI-PDFF (MRI-Proton Density Fat Fraction). A value of >5.2% will be considered the threshold for development of NAFLD following LT.

Change in adiposity

Fat distribution of the body body (body composition) will be assessed via MRI (i.e. visceral adipose tissue, abdominal subcutaneous tissue, fat free muscle volume, and muscle fat infiltration, epicardial fat). Means of delta body composition measures after 72 weeks will be compared between the two arms.

Change in insulin resistance

Frequently Sampled IV Glucose Tolerance Test (FSIVGTT) will be used to measure insulin resistance

Change in inflammation - C-reactive protein (CRP)

Level of CRP will be assessed using a standard blood test.

Change in inflammation - adiponectin

Level of adiponectin will be assessed using a standard blood test.

Change in liver fibrosis markers

Fibrosis-4 (FIB-4) Index for Liver Fibrosis and NAFLD Fibrosis Score (NFS) will be assessed using a standard blood test.

Change in serum lipid profile

Cardiovascular risk factors will be assessed using a standard lipid panel blood test.

Full Information

NCT ID

NCT05424003

First Posted

June 14, 2022

Last Updated

October 10, 2023

Sponsor

Virginia Commonwealth University

Collaborators

Novo Nordisk A/S

1. Study Identification

Unique Protocol Identification Number

NCT05424003

Brief Title

Randomized Double Blinded Placebo-Controlled w/Semaglutide to Prevent Weight Gain After Liver Transplant

Official Title

A Randomized Double Blinded Placebo-Controlled Trial of Semaglutide to Prevent Weight Gain Following Liver Transplantation

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

November 2023 (Anticipated)

Primary Completion Date

February 2026 (Anticipated)

Study Completion Date

February 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Virginia Commonwealth University

Collaborators

Novo Nordisk A/S

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

In this study, semaglutide will be compared to placebo (a look-alike inactive substance, a "sugar pill") to determine if its use will prevent weight gain after liver transplantation (LT). In addition, researchers will be testing to determine if semaglutide prevents the development of Non-Alcoholic Fatty Liver Disease (NAFLD) after transplant through Magnetic Resonance Imaging (MRI) and laboratory results.

Detailed Description

Weight gain following LT is common and a risk for cardiovascular disease and development of NAFLD. Developing NAFLD following LT can lead to patients developing scar tissue in the graft (transplanted liver), and graft-cirrhosis. These events can limit the benefit of the transplanted liver graft and reduce the benefit of LT as a therapy. Current weight management strategies have not been successful at the prevention of these events in most patients. This highlights a substantial unmet need for effective treatment to prevent or reduce post-LT weight gain and highlight the importance of new treatment strategies for reducing illness, death, and healthcare cost associated with post-LT weight gain. The purpose of this research study is to test the safety, tolerability, and effectiveness of semaglutide when used to prevent weight gain after liver transplant. Semaglutide is a drug that has been approved by the U. S. Food and Drug Administration (FDA) for treatment of obesity and Type 2 Diabetes. Semaglutide, has shown to be effective for not only weight loss but also long-term weight maintenance. Semaglutide has also shown to be helpful in treatment of nonalcoholic steatohepatitis (NASH) in the non-transplant population. This medication also is used to control blood sugar and prevent cardiovascular disease, which contributes to poor outcomes in LT recipients. Thus, the purpose of the present study is to determine if use of semaglutide early after LT can (1) reduce weight gain and (2) prevent development of NAFLD following LT.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

NAFLD

Keywords

Liver Transplant

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Semaglutide

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo administered subcutaneously (under the skin) once weekly.

Intervention Type

Drug

Intervention Name(s)

Semaglutide Pen Injector

Other Intervention Name(s)

Wegovy

Intervention Description

Starting dose of 0.24 mg injected weekly and increased every 4 weeks to a potential maximum dose of 2.4 mg weekly at 20 weeks followed by 52 weeks of weekly injections at the maximum tolerable dose

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo solution injected weekly for 72 weeks

Primary Outcome Measure Information:

Title

Change in weight

Description

Weight measured in kilograms

Time Frame

Baseline to week 72

Secondary Outcome Measure Information:

Title

Development of NAFLD

Description

Time Frame

Week 72

Title

Change in adiposity

Description

Time Frame

Baseline to week 72

Title

Change in insulin resistance

Description

Frequently Sampled IV Glucose Tolerance Test (FSIVGTT) will be used to measure insulin resistance

Time Frame

Baseline to week 72

Title

Change in inflammation - C-reactive protein (CRP)

Description

Level of CRP will be assessed using a standard blood test.

Time Frame

Baseline to week 72

Title

Change in inflammation - adiponectin

Description

Level of adiponectin will be assessed using a standard blood test.

Time Frame

Baseline to week 72

Title

Change in liver fibrosis markers

Description

Fibrosis-4 (FIB-4) Index for Liver Fibrosis and NAFLD Fibrosis Score (NFS) will be assessed using a standard blood test.

Time Frame

Baseline to week 72

Title

Change in serum lipid profile

Description

Cardiovascular risk factors will be assessed using a standard lipid panel blood test.

Time Frame

Baseline to week 72

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female age 18-75 years who received LT for any indication (i.e. NASH, hepatitis C, alcohol-induced cirrhosis, autoimmune hepatitis, etc.) Liver transplant surgery within 8-24 weeks prior to randomization Presence of diabetes (HbA1c≥6.5% or use of diabetes medications) or pre-diabetes (HbA1c >5.7%) Ability to provide informed consent Discharged from the hospital following LT surgery Tolerating diet Normal graft function* (determined by treating hepatologist/surgeon based on clinical status and hepatic panel) Stable immunosuppression according the VCU (Virginia Commonwealth University) post-LT protocols ** (i.e. calcineurin inhibitors + mycophenolate) Eligible female patients will be (1) non-pregnant, evidenced by a negative urine pregnancy test, (2) non-lactating, (3)surgically sterile or post-menopausal, or they will agree to continue to use an accepted method of birth control during the study Exclusion Criteria: BMI≤ 27kg/m2 GFR (Glomerular Filtration Rate) ≤ 25 ml/min/1.73m2 Type 1 autoimmune diabetes (by anti-GAD (glutamic acid decarboxylase) or history of ketoacidosis) History of gastroparesis Familial or personal history of medullary thyroid cancer or MEN (Multiple Endocrine Neoplasia) 2 History of pancreatitis History of active malignancy post- LT with the exception of non-melanoma skin cancers History of uncontrolled or unstable diabetic retinopathy or maculopathy Acute cellular rejection Hepatic artery thrombosis Medical non-compliance Active treatment with GLP (glucagon-like peptide)-1RA (receptor agonist) or SGLT (sodium-glucose cotransporter)-2 inhibitors at time of screening History of hypersensitivity to semaglutide or its excipients Women who are nursing, pregnant, or planning to become pregnant during the study, or are not using adequate contraceptive measures

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sherry Boyett, RN

Phone

804-828-5434

sherry.boyett@vcuhealth.org

First Name & Middle Initial & Last Name or Official Title & Degree

Mohammad S Siddiqui, MD

mohammad.siddiqui@vcuhealth.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mohammad S Siddiqui, MD

Organizational Affiliation

Virginia Commonwealth University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Virginia Commonwealth University

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23298

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Randomized Double Blinded Placebo-Controlled w/Semaglutide to Prevent Weight Gain After Liver Transplant

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