Weight Management for Obesity and Kidney Disease

Recruiting in Palo Alto (17 mi)

Overseen by Kristin K Clemens, MD, MSc

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Western University, Canada

Must not be taking: Semaglutide, Liraglutide, Dulaglutide

Disqualifiers: Type 1 diabetes, Pregnancy, others

No Placebo Group

Prior Safety Data

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

OK-TRANSPLANT 2 is a vanguard study for a large randomized, pragmatic, open-label trial. We will randomize participants with obesity, high-risk CKD/dialysis who are hoping for lose weight for the purpose of kidney transplant. Subjects will either be enrolled on a virtual weight management program or continue their usual care.

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 are using more than the starting dose of certain medications like semaglutide, liraglutide, or dulaglutide.

What data supports the effectiveness of the drug Semaglutide for weight management in patients with obesity and kidney disease?

Research shows that Semaglutide, a drug used for diabetes, can help with weight loss and improve kidney function in people with obesity and kidney disease. It has been effective in reducing body weight and managing blood sugar levels, which can be beneficial for patients with these conditions.

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Is the treatment safe for humans?

Semaglutide, marketed under names like Rybelsus, Ozempic, and Wegovy, has been shown to be safe in humans, including those with type 2 diabetes and chronic kidney disease. It is generally well-tolerated and has a good safety profile, with benefits such as weight loss and cardiovascular protection.

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How is the drug Semaglutide unique for treating obesity and kidney disease?

Semaglutide is unique because it is a once-weekly injection that not only helps with weight loss but also improves kidney function by reducing albuminuria (protein in urine) and preserving kidney function, which is particularly beneficial for patients with chronic kidney disease.

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Eligibility Criteria

This trial is for individuals with obesity and high-risk chronic kidney disease (CKD) or those on dialysis, aiming to lose weight for a kidney transplant. Participants must be seeking to manage their weight and willing to engage in a virtual program.

Inclusion Criteria

I am at high risk for severe kidney failure or am on dialysis.

I am 18 years old or older.

BMI > 35 kg/m^2

Exclusion Criteria

I do not have insurance coverage for semaglutide.

I have Type 1 diabetes.

I cannot have a kidney transplant due to health reasons.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vanguard Phase

Feasibility study to ensure recruitment and process inclusivity, and assess program acceptability

12 months

Treatment

Participants receive either usual care or a virtual weight management program with semaglutide and coaching

26 weeks

Virtual coaching once every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Participant Groups

The OK-TRANSPLANT 2 study is testing the effectiveness of virtual weight management coaching compared to usual care practices. Additionally, it will evaluate the use of Semaglutide, a medication that may aid in weight loss.

Group I: Virtual Weight Management Program Experimental Treatment 2 Interventions

A maximum tolerated dose of semaglutide (Ozempic/Wegovy) will be administered once weekly subcutaneously, up to a dose of 2.0 mg. Participants will also receive nutritional and movement advice, as well as virtual coaching once every 4 weeks for 6 months.

Group II: Usual Care Active Control 1 Intervention

Usual care participants will continue to receive the typical standard of kidney and diabetes care. They will not receive any study medication or coaching.

Semaglutide is already approved in European Union, United States, Canada, Japan, United States, United States 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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

London Health Sciences Centre London, Canada

Who Is Running the Clinical Trial?

Western University, Canada Lead Sponsor

Lawson Health Research Institute Collaborator

Unity Health Toronto Collaborator

Queen Elizabeth II Health Sciences Centre Collaborator

St. Michael's Hospital (Toronto, Canada) Collaborator

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's Collaborator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's Collaborator

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's Collaborator

References

1. United States pubmed.ncbi.nlm.nih.gov

Effects of Semaglutide on Albuminuria and Kidney Function in People With Overweight or Obesity With or Without Type 2 Diabetes: Exploratory Analysis From the STEP 1, 2, and 3 Trials. [2023] These post hoc analyses of the Semaglutide Treatment Effect in People with obesity (STEP) 1-3 trials (NCT03548935, NCT03552757, and NCT03611582) explored the effects of semaglutide (up to 2.4 mg) on kidney function.

2. Switzerland 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. [2022] The glucagon-like peptide-1 receptor agonists (GLP-1RA) are among the newest treatment options available for managing of type 2 diabetes mellitus and slowing the progression of diabetes kidney disease (DKD). Subcutaneous (SC) semaglutide (Ozempic®) is a GLP-1RA with an extended half-life of approximately 1 week. GLP-1RA are highly effective in improving glycemic control and also show other beneficial effects such as increased natriuresis; decreased blood pressure and albuminuria; reduction of oxidative stress and inflammation; delay of gastric emptying and suppress appetite; the latter may result in significant weight loss. GLP-1RA can be used in patients with advanced-stage CKD; the European Medicines Agency has approved the use of all commercially available human GLP-1 analogs up to a minimal eGFR of 15 mL/min/1.73 m2. However, studies of safety and use of these agents in renal replacement therapy are scarce. Therefore, herein we present 3 cases of patients with advanced DKD in maintenance incremental hemodialysis with 1 session per week to describe the efficacy and safety of the SC semaglutide treatment and the favorable effects on glycemic control, lowering HbA1c, albuminuria, weight, blood pressure control, and preservation of residual kidney function (RKF) during a 6-month follow-up in a hospital hemodialysis unit in Spain. These effects could produce an improvement in morbidity and mortality and could also prevent albuminuria and preserve the RKF. This may allow our patients to maintain a weekly hemodialysis session and could facilitate their inclusion in the kidney transplant waiting lists.

3. England pubmed.ncbi.nlm.nih.gov

Semaglutide for treatment of obesity in hemodialysis patients waiting for a kidney transplant: new hope? [2022] Obesity limits the access to kidney transplantation and increases the risk of complications and mortality posttransplantation. Usual noninvasive measures, including lifestyle changes and dietary education, do not provide long-term and consistent body weight reduction. In many cases, only bariatric surgery allows patients to significantly reduce body weight. We here report two cases of obese hemodialysis (HD) patients who were successfully treated with off-labeled semaglutide, a glucagon-like peptide receptor agonist (GLP-1RA). The first patient had a body mass index (BMI) of 45.7 kg/m2 despite a history of partial gastrectomy. The second patient had a history of type 2 diabetes mellitus and a BMI of 36.5 kg/m2. Both patients started semaglutide at the maximal subcutaneous dose of 1 mg/week, which was clinically well tolerated. During the 9-month follow-up, body weight loss ranged from 6.5 to 9.0 kg, ∼1 kg/month. GLP-1RAs, such as semaglutide or liraglutide, could be a novel pharmacological alternative to bariatric surgeries for these HD patients.

4. Switzerland pubmed.ncbi.nlm.nih.gov

Influence of chronic kidney disease and its severity on the efficacy of semaglutide in type 2 diabetes patients: a multicenter real-world study. [2023] Semaglutide is a glucagon-like peptide 1 receptor agonist that improves glycemic control and achieves weight loss in type 2 diabetes (T2D) patients. Subcutaneous (s.c.) semaglutide at 1 mg once weekly (OW) is safe in T2D patients with chronic kidney disease (CKD). Whether or not CKD and its severity influence treatment response remains undetermined.

5. England 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. [2020] Patients with type 2 diabetes have a high risk of developing chronic kidney disease. We examined the effects of semaglutide on kidney function and safety in a large, broad type 2 diabetes population.

6. Belgium pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. [2022] Oral semaglutide (Rybelsus®) is a co-formulation of semaglutide, a glucagon-like peptide-1 (GLP-1 RA) receptor agonist, with an absorption enhancer, sodium N- (8- [2- hydroxybenzoyl] amino) caprylate (SNAC), which facilitates the absorption of semaglutide across the gastric epithelium in a concentration dependent manner. The safety and efficacy of oral semaglutide were assessed in the PIONEER clinical trial programme, which included 9543 patients with type 2 diabetes (T2DM). Across a range of different T2DM patients receiving different background medications, oral semaglutide provides more effective glycaemic control than common oral glucose-lowering therapies, associated with a clinically relevant reduction in body weight, including in patients with more advanced T2DM on insulin treatment. The tolerability profile for oral semaglutide was consistent with the other GLP-1 RAs. Cardiovascular (CV) safety of oral semaglutide was noninferior to placebo in CV high-risk patients. Available in three doses (3, 7 and 14 mg) to be gradually increased, Rybelsus® is currently reimbursed in Belgium after failure of antidiabetic treatment (including metformin; HbA1C superior to 7.5 % or 58 mmol/mol) in T2DM patients with a body mass index ? 30 kg/m².

7. New Zealand pubmed.ncbi.nlm.nih.gov

A Peptide in a Pill - Oral Semaglutide in the Management of Type 2 Diabetes. [2023] T2DM (type 2 diabetes mellitus) is a chronic and progressive illness with high morbidity and death rates. Oral semaglutide (Rybelsus®) is a combination of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), and sodium N- (8- [2-hydroxybenzoyl] amino) caprylate (SNAC), an absorption enhancer that facilitates semaglutide absorption across the gastric epithelium in a concentration-dependent manner. This family of drugs apart from glucose lowering effects causes significant weight loss with lower risk of hypoglycemia, and some of them have been linked to a significant reduced major adverse cardiovascular events. GLP-1 RAs may assist persons with T2DM and chronic kidney disease (CKD), a major microvascular consequence of T2DM, in ways other than lowering blood sugar. Several large clinical studies, the bulk of which are cardiovascular outcome trials, show that GLP-1 RA treatment is safe and tolerated for persons with T2DM and impaired renal function and that it may potentially have renoprotective characteristics. This article focuses on the advances of oral GLP1-RA and describes the key milestones and predicted advantages.

8. United States pubmed.ncbi.nlm.nih.gov

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. [2021] Semaglutide is an oral glucagon-like peptide receptor agonist approved in 2019 by the U.S. Food and Drug Administration. It is marketed under the brand name Rybelsus and was approved to be used in conjunction with lifestyle modifications to treat individuals with type 2 diabetes. It is the first in its drug class to be administered in a once-daily oral form. Through its actions on glucose control and body weight, this once-daily oral medication could contribute to better glycemic control and healthier lives for many women with type 2 diabetes.

9. Spain 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. [2023] Diabetic kidney disease, a common complication in patients with type 2 diabetes mellitus, is associated with a markedly increased morbidity and mortality, especially of cardiovascular origin, and faster progression to end-stage renal disease. To date, reducing cardiovascular and renal risk in this population was based on strict control of cardiovascular risk factors and the renin-angiotensin system blockade. More recently, sodium-glucose cotransporter type 2 inhibitors have demonstrated to offer cardiovascular and renal protection, but the residual risk remains high and their antihyperglycemic efficacy is limited in moderate-severe CKD. Therefore, drugs with a potent antihyperglycemic effect, independent of the glomerular filtration rate, with a low risk of hypoglycemia, that reduce weight in overweight/obese patients and that provide cardiovascular and renal protection, such as GLP-1 receptor agonists, are needed. However, these drugs require subcutaneous administration, which may limit their early use. The recent availability of oral semaglutide may facilitate the early introduction of this family with proven cardiovascular and renal benefits and excellent safety profile. In this review the family is analyzed as well as their cardiovascular and renal effects.

10. Belgium pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. [2019] Semaglutide (Ozempic®) is a new once-weekly agonist of glucagon-like peptide-1 receptors (GLP-1 AR) indicated in the treatment of type 2 diabetes (T2D). Phase III clinical trials of the SUSTAIN programme demonstrated both the efficacy and safety of semaglutide in patients with T2D treated by diet and exercise, oral antidiabetic agents or even insulin. Direct and indirect comparative clinical trials showed that semaglutide (subcutaneous 0.5 or 1.0 mg once weekly) exerts a better glucose-lowering activity and a greater weight loss than other GLP-1 AR. Presented as prefilled pens for subcutaneous injection, semaglutide is currently reimbursed in Belgium after failure of antidiabetic therapy including metformin (HbA1c superior to 7,5 % or 58 mmol/mol) in T2D patients with body mass index ? 30 kg/m².