NAFLDPhase 2NCT05424003
Randomized Double Blinded Placebo-Controlled w/Semaglutide to Prevent Weight Gain After Liver Transplant
A Phase 2 study testing Semaglutide Pen Injector in people with NAFLD, run by University of Virginia at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- NAFLD
- What is being tested?
- Semaglutide Pen Injector
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Feb 2024to 1 Aug 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Fasting glucose > 125 mg/dL or 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Mohammad S Siddiqui, MD contact
United States1 site, 1 recruiting
- Recruiting
Virginia Commonwealth University
Richmond, Virginia, 23298
About this study
Official title: A Randomized Double Blinded Placebo-Controlled Trial of Semaglutide to Prevent Weight Gain Following Liver Transplantation
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.
Read the 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.
- Conditions
- NAFLD
- Being tested
- Semaglutide Pen Injector, Placebo
- Keywords
- Liver Transplant
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Semaglutide Pen InjectorDrug
Also called Wegovy
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
PlaceboDrug
Placebo solution injected weekly for 72 weeks
| Study group | Role | What they receive |
|---|---|---|
| Semaglutide | Experimental | 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. Receives: Drug: Semaglutide Pen Injector |
| Placebo | Placebo comparator | Placebo administered subcutaneously (under the skin) once weekly. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in weight
Weight measured in kilograms
Measured: Baseline to week 72
Secondary outcomes (7)
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.
Measured: Week 72
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.
Measured: Baseline to week 72
Change in insulin resistance
Frequently Sampled IV Glucose Tolerance Test (FSIVGTT) will be used to measure insulin resistance
Measured: Baseline to week 72
Change in inflammation - C-reactive protein (CRP)
Level of CRP will be assessed using a standard blood test.
Measured: Baseline to week 72
Change in inflammation - adiponectin
Level of adiponectin will be assessed using a standard blood test.
Measured: Baseline to week 72
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.
Measured: Baseline to week 72
Change in serum lipid profile
Cardiovascular risk factors will be assessed using a standard lipid panel blood test.
Measured: Baseline to week 72
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2022
- Study start22 Feb 2024
- Primary completion1 Aug 2026 (estimated)
- Study completion1 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NAFLDStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- Novo Nordisk A/S
- Responsible party
- Principal investigator, Mohammad Siddiqui, University of Virginia
- Investigators
- Mohammad S Siddiqui, MD, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05424003
- Sponsor's protocol ID
- HM20024306
- Status last verified
- Jun 2026
- First submitted
- 14 Jun 2022
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double Blinded Placebo-Controlled Trial of Semaglutide to Prevent Weight Gain Following Liver Transplantation
- ClinicalTrials.gov ID
- NCT05424003
- Acronym / sponsor ID
- HM20024306
- Conditions
- NAFLD
- Keywords
- Liver Transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- Novo Nordisk A/S
- Study start
- 22 Feb 2024 (actual)
- Primary completion
- 1 Aug 2026 (estimated)
- Study completion
- 1 Aug 2026 (estimated)
- First posted
- 21 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Semaglutide | Experimental | Drug: Semaglutide Pen InjectorSemaglutide 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 | Placebo comparator | Drug: PlaceboPlacebo administered subcutaneously (under the skin) once weekly. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
- Fasting glucose > 125 mg/dL or 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Semaglutide Pen InjectorAlso: WegovyStarting 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 | Drug | Semaglutide |
| PlaceboPlacebo solution injected weekly for 72 weeks | Drug | Placebo |
Primary outcome
Change in weight
Time frame: Baseline to week 72
Weight measured in kilograms
7 secondary outcomes
Development of NAFLD
Time frame: Week 72
Change in adiposity
Time frame: Baseline to week 72
Change in insulin resistance
Time frame: Baseline to week 72
Change in inflammation - C-reactive protein (CRP)
Time frame: Baseline to week 72
Change in inflammation - adiponectin
Time frame: Baseline to week 72
Change in liver fibrosis markers
Time frame: Baseline to week 72
Change in serum lipid profile
Time frame: Baseline to week 72
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mohammad S Siddiqui, MD contact
Mohammad S Siddiqui, MD principal investigator
Virginia Commonwealth University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Semaglutide Pen Injector in people with NAFLD, run by University of Virginia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sherry Boyett, RN (804-828-5434, sherry.boyett@vcuhealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in weight (time frame: Baseline to week 72). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2026.