Semaglutide for Polycystic Kidney Disease

Overseen By Diana George

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must be taking: Glucagon-like peptide 1

Must not be taking: Tolvaptan, Weight-affecting drugs

Disqualifiers: Diabetes, Hypertension, Eating disorders, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

126 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called semaglutide to determine if it can slow kidney growth in individuals with polycystic kidney disease who are overweight or obese. Researchers aim to discover whether semaglutide, typically used for weight management and improving blood sugar levels, can also enhance kidney health. The trial will examine changes in belly fat and kidney metabolism using advanced imaging techniques. Ideal participants are adults diagnosed with polycystic kidney disease, with a BMI over 27, and not currently enrolled in a weight loss program. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you regularly use medications that affect weight, appetite, food intake, or energy metabolism.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that semaglutide is generally well-tolerated by people with chronic kidney problems. In one study, fewer serious side effects occurred in those taking semaglutide compared to those taking a placebo. Specifically, 49.6% of people on semaglutide experienced these side effects, while 53.8% of those on the placebo did. This suggests semaglutide may be safe to use.

Semaglutide is also approved for other uses, such as weight management, indicating it has been tested for safety in different conditions. In these studies, semaglutide helped reduce risks related to kidney problems, supporting its potential safety and benefits for people with kidney conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for polycystic kidney disease, which often focus on managing symptoms like high blood pressure and pain, semaglutide offers a novel approach by targeting the underlying metabolic pathways involved in the disease. Researchers are excited about semaglutide because it's a GLP-1 receptor agonist, a type of drug usually used to treat diabetes and obesity, which could potentially slow down the progression of kidney damage. Its unique mechanism of action not only helps control blood sugar levels but may also protect kidney function, offering hope for a more comprehensive treatment option for patients with this condition.

What evidence suggests that this trial's treatments could be effective for polycystic kidney disease?

Research has shown that semaglutide, a medication commonly used for diabetes and weight management, might also help with kidney problems. In people with type 2 diabetes and chronic kidney disease, semaglutide lowered the risk of serious kidney issues. One study found a 24% decrease in major kidney disease events. Although this trial focuses on patients with polycystic kidney disease, these results suggest semaglutide could help slow kidney problems. Participants in this trial will receive either semaglutide or a placebo. The drug helps the body manage sugar and insulin better, which might aid in controlling kidney growth and function. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

Adults aged 18-65 with autosomal dominant polycystic kidney disease (ADPKD), overweight or obese, and a reasonable level of kidney function. Participants should not be in other weight loss programs or clinical studies and must have had a recent ultrasound or MRI.

Inclusion Criteria

ADPKD diagnosis based on the modified Pei-Ravine criteria

Body-mass index of ≥27 kg/m^2

Ability to provide informed consent

Exclusion Criteria

Uncontrolled hypertension (systolic blood pressure > 160 or diastolic blood pressure >100 mm Hg)

I have not been hospitalized or had major surgery in the last 3 months.

Inability to cooperate with or clinical contraindication for MRI including: severe claustrophobia, implants, devices, or non-removable body piercings

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a glucagon-like peptide 1 receptor agonist or placebo for 12 months to assess its efficacy in slowing kidney growth in ADPKD patients

12 months

Weekly visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Semaglutide

Trial Overview

The trial is testing Semaglutide, a drug used for weight management that may slow kidney growth in ADPKD patients. It compares the effects of this drug to a placebo over two years, using advanced imaging to monitor changes.

How Is the Trial Designed?

Group I: Tirzepatide Experimental Treatment 1 Intervention

To minimize the risk of gastrointestinal adverse events, we will use a standard dose-escalation regimen for tirzepatide (placebo-matched), starting at 2.5 mg once weekly (OW) at randomization. After 4 weeks of treatment at 2.5 mg, the dose will be escalated to 5 mg OW, which will be maintained for another 4 weeks and then continued as the target dose for 10 months until the end of treatment. As with other nutrient stimulating hormone (NuSH) therapies, dose reductions and extensions of dose-escalation intervals will be permitted if participants experience unacceptable adverse events. The minimum tolerated dose required for continued study participation is 2.5 mg/week. All dose changes will be documented in the study records.

Group II: Placebo Placebo Group 1 Intervention

To minimize the risk of gastrointestinal adverse events, we will use a standard dose-escalation regimen for tirzepatide (placebo-matched), starting at 2.5 mg once weekly (OW) at randomization. After 4 weeks of treatment at 2.5 mg, the dose will be escalated to 5 mg OW, which will be maintained for another 4 weeks and then continued as the target dose for 10 months until the end of treatment. As with other nutrient stimulating hormone (NuSH) therapies, dose reductions and extensions of dose-escalation intervals will be permitted if participants experience unacceptable adverse events. The minimum tolerated dose required for continued study participation is 2.5 mg/week. All dose changes will be documented in the study records.

Semaglutide is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Canada as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Japan as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Wegovy for:

• Obesity

Approved in United States as Rybelsus for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

Subcutaneous semaglutide (Ozempic®), a GLP-1 receptor agonist, has shown significant efficacy in improving glycemic control and reducing HbA1c, albuminuria, and blood pressure in patients with advanced diabetic kidney disease (DKD) during a 6-month follow-up study involving patients on maintenance hemodialysis.

The treatment not only aids in weight loss and appetite suppression but also helps preserve residual kidney function, potentially improving patient outcomes and facilitating their inclusion on kidney transplant waiting lists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Semaglutide, a Glucagon-Like Peptide-1 Receptor Agonist in Real-Life: A Case Series of Patients in Maintenance Incremental Hemodialysis. De la Flor, JC., Lorenzo, JD., Marschall, A., et al.[2022]

Oral semaglutide (Rybelsus®), a GLP-1 receptor agonist, not only helps lower blood sugar levels in people with type 2 diabetes but also promotes significant weight loss and has a lower risk of causing hypoglycemia.

Clinical studies indicate that GLP-1 receptor agonists are safe for individuals with type 2 diabetes and chronic kidney disease, and they may offer additional benefits such as protecting kidney function and reducing the risk of major cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Peptide in a Pill - Oral Semaglutide in the Management of Type 2 Diabetes. Selvarajan, R., Subramanian, R.[2023]

In a study involving 56 subjects with varying degrees of renal impairment, semaglutide exposure was found to be similar in those with mild to moderate renal impairment and end-stage renal disease compared to those with normal kidney function, suggesting it is safe for use in these populations.

The drug was well-tolerated overall, with no significant safety concerns or serious adverse events reported, indicating that dose adjustments for semaglutide may not be necessary for patients with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Tolerability of a Single Dose of Semaglutide, a Human Glucagon-Like Peptide-1 Analog, in Subjects With and Without Renal Impairment. Marbury, TC., Flint, A., Jacobsen, JB., et al.[2018]

Oral semaglutide, a GLP-1 analogue, showed consistent pharmacokinetics across various levels of renal impairment in a trial involving 71 subjects, indicating that kidney function does not significantly affect its absorption or metabolism.

The study found no safety concerns associated with oral semaglutide, and adverse events were similar to those seen with other GLP-1 receptor agonists, suggesting it is safe for use in patients with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety and Tolerability of Oral Semaglutide in Subjects with Renal Impairment. Granhall, C., Søndergaard, FL., Thomsen, M., et al.[2021]

In a post-hoc analysis of 8416 patients with type 2 diabetes from multiple trials, semaglutide initially caused a decline in estimated glomerular filtration rate (eGFR), but this decline plateaued over time, indicating no long-term adverse effects on kidney function compared to placebo.

Semaglutide significantly reduced urinary albumin-to-creatinine ratio (UACR), suggesting improved kidney health, and there was no increase in kidney-related adverse events compared to other treatments, highlighting its safety and efficacy in managing kidney function in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of once-weekly subcutaneous semaglutide on kidney function and safety in patients with type 2 diabetes: a post-hoc analysis of the SUSTAIN 1-7 randomised controlled trials. Mann, JFE., Hansen, T., Idorn, T., et al.[2020]

Semaglutide (Ozempic®) is an effective once-weekly treatment for type 2 diabetes, showing superior glucose-lowering effects and greater weight loss compared to other GLP-1 receptor agonists in Phase III clinical trials.

It is approved for use in Belgium for patients with type 2 diabetes who have not achieved adequate control with other antidiabetic therapies, particularly in those with a body mass index of 30 kg/m² or higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. Scheen, AJ.[2019]

Oral semaglutide (Rybelsus®) has been shown to provide better glycaemic control and promote weight loss in patients with type 2 diabetes (T2DM) compared to standard oral glucose-lowering medications, based on data from the PIONEER clinical trial program involving 9543 patients.

The safety profile of oral semaglutide is similar to other GLP-1 receptor agonists, and it demonstrated cardiovascular safety comparable to placebo in high-risk patients, making it a viable option for T2DM management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. Paquot, N.[2022]

Sodium-glucose cotransporter type 2 (SGLT2) inhibitors provide cardiovascular and renal protection for patients with diabetic kidney disease, but there is still a high residual risk and limited effectiveness in moderate to severe chronic kidney disease (CKD).

Oral semaglutide, a GLP-1 receptor agonist, offers a promising alternative with potent antihyperglycemic effects, low risk of hypoglycemia, and cardiovascular and renal benefits, potentially improving early treatment options for patients with type 2 diabetes and diabetic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide 1(GLP-1) receptor agonists in the management of the patient with type 2diabetes mellitus and chronic kidney disease: an approach for the nephrologist. Cases, A.[2023]

Oral semaglutide, a new GLP-1 receptor agonist, significantly reduced glycated hemoglobin (HbA1c) levels by up to 1.4% after 26 weeks compared to placebo, indicating its efficacy in managing blood sugar levels in type 2 diabetes patients.

The treatment also led to greater body weight reductions compared to placebo and sitagliptin, with mild-to-moderate gastrointestinal side effects that typically decreased over time, suggesting it is a safe option with a low risk of severe hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical review of the efficacy and safety of oral semaglutide in patients with type 2 diabetes compared with other oral antihyperglycemic agents and placebo. Lavernia, F., Blonde, L.[2022]

In a study involving diabetic db/db mice with advanced diabetic kidney disease (DKD), the GLP-1 receptor agonist semaglutide significantly reduced hyperglycemia, hypertension, and albuminuria, while improving kidney health markers such as glomerulosclerosis and podocyte density.

The combination of semaglutide with the ACE inhibitor lisinopril provided additional benefits in managing hypertension and kidney damage, suggesting that semaglutide could be an effective treatment option for patients with DKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nephroprotective Effects of Semaglutide as Mono- and Combination Treatment with Lisinopril in a Mouse Model of Hypertension-Accelerated Diabetic Kidney Disease. Dalbøge, LS., Christensen, M., Madsen, MR., et al.[2022]

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Semaglutide reduced the risk of the primary kidney outcome by 49% (59 events; hazard ratio [HR] 0.51 [95% CI 0.30, 0.86]) and 21% (682 events; ...

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In a real-world setting, oral semaglutide treatment for up to 52 weeks resulted in clinically meaningful reductions in albuminuria without ...