SLIMM + Semaglutide for Kidney Disease

Recruiting at 1 trial location

Overseen By Srinivasan Beddhu, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Srinvasan Beddhu

Must be taking: Semaglutide

Must not be taking: GLP-1 receptor agonists

Disqualifiers: Type 1 diabetes, Bariatric surgery, Heart failure, others

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

Compensation: Varies

Number of Visits: Unknown

156 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores ways to reduce sedentary behavior in people with kidney disease. Researchers aim to determine if combining guided resistance training (to build muscle) with semaglutide (a diabetes and weight loss medication that might enhance physical activity) can encourage participants to maintain an active lifestyle. Participants are divided into three groups: one with standard resistance training and a placebo, another with guided resistance training and a placebo, and a third with guided resistance training and semaglutide. The study also incorporates the SLIMM approach (Sit Less, Interact and Move More) to promote an active lifestyle. Individuals with chronic kidney disease who can perform resistance training and have a smartphone or similar device may be suitable for this study. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant findings.

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 use any GLP-1 receptor agonist within 30 days before joining the study.

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

Research has shown that semaglutide is generally safe for people. The FDA has approved this medication for treating diabetes and aiding weight loss, indicating it has passed strict safety tests for these uses. Some individuals might experience side effects like nausea or mild digestive issues, but these are usually manageable.

In the SLIMM approach, no major safety issues have been reported. This method encourages people to sit less, which can improve overall health. The study also includes guided resistance training, a common exercise routine to build strength, which is usually safe when performed correctly.

The study is in Phase 2, which tests the treatment's effectiveness and safety. This phase typically involves more participants than earlier stages, suggesting that initial safety data is promising, but more information is being collected. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for kidney disease because they combine unique approaches with existing methods. Unlike standard treatments that often focus solely on standard-of-care medications, the SLIMM protocol integrates a specialized lifestyle intervention with resistance training, aiming to enhance kidney function and overall health. The addition of Semaglutide, a medication typically used for diabetes, introduces a novel mechanism by potentially improving metabolic health and kidney outcomes. This combination offers a fresh perspective on managing kidney disease, with the potential to improve patient outcomes beyond what current treatments achieve.

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

Research has shown that the SLIMM (Sit Less, Interact, and Move More) program can help people reduce sitting time, which is linked to better kidney health and a lower risk of diabetes and heart disease. However, maintaining these benefits over time has proven challenging. In this trial, one group of participants will receive SLIMM combined with guided resistance training and semaglutide. Studies have found that semaglutide improves kidney health and reduces risks related to diabetes and heart problems. It also aids in weight loss and blood sugar control, which may further benefit kidney health. Together, SLIMM and semaglutide aim to reduce sitting time and improve overall health in people with kidney disease. ^{1 2 3 4 6}

Who Is on the Research Team?

Srinivasan Beddhu, M.D.

Principal Investigator

University of Utah

Are You a Good Fit for This Trial?

The SLIMM 2 study is for adults with chronic kidney disease who are overweight, can walk a certain distance, and have moderate to severe reduction in kidney function. Participants need internet access and the ability to do resistance training but cannot be on oxygen therapy or have had recent major medical procedures.

Inclusion Criteria

Access to compatible "smartphone" or device (i.e., Android, Kindle or Apple with internet connectivity or mobile network), desktop or laptop

I can walk between 300 to 600 meters in six minutes.

My kidney function is moderately to severely reduced.

Exclusion Criteria

Vulnerable populations- pregnant or incarcerated

I use supplemental oxygen during the day.

I use devices like canes or walkers to help me move around.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

SLIMM Intervention

Participants undergo the SLIMM intervention targeting sedentary behavior

3 months

Extended Intervention

Participants continue with SLIMM, resistance training, and either placebo or semaglutide

9 months

Follow-up

Participants are monitored for changes in sleep, quality of life, inflammation markers, and physical performance

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Guided Resistance Training
• Placebo
• Semaglutide
• SLIMM
• Standard Resistance Training

Trial Overview

This trial tests whether guided resistance training and semaglutide (a diabetes/weight loss medication) can help people with kidney disease reduce sedentary behavior by improving muscle strength and physical function as part of the SLIMM intervention.

How Is the Trial Designed?

Group I: SLIMM + Guided RT + Semaglutide Experimental Treatment 3 Interventions

SLIMM intervention for 3 months, followed by a 9-month intervention of SLIMM, guided resistance training and oral semaglutide

Group II: SLIMM + Guided RT + Placebo Active Control 3 Interventions

SLIMM intervention for 3 months, followed by a 9-month intervention of SLIMM, guided resistance training and oral placebo

Group III: SLIMM + Standard RT + Placebo Placebo Group 3 Interventions

SLIMM intervention for 3 months, followed by a 9-month intervention of SLIMM, standard-of-care resistance training and oral placebo

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?

Srinvasan Beddhu

Lead Sponsor

Trials

3

Recruited

290+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

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 (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]

In a study involving 486 type 2 diabetes patients, semaglutide was found to be effective in improving glycemic control and achieving weight loss, with no significant differences in efficacy between patients with chronic kidney disease (CKD) and those without.

The treatment was safe for all patients, and CKD severity did not notably affect the treatment response, suggesting that semaglutide can be effectively used in managing type 2 diabetes in patients with varying levels of kidney function.

NCBI (Pubmed)

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. García de Lucas, MD., Caballero, I., Fernández-García, JC., et al.[2023]

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]

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, 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]

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]

In the STEP 2 trial involving 1,205 participants, semaglutide (both 1.0 mg and 2.4 mg) significantly improved kidney function as measured by urine albumin-to-creatinine ratio (UACR), with reductions of -14.8% and -20.6% respectively, compared to an increase of +18.3% in the placebo group.

Across pooled data from STEP 1-3, semaglutide did not affect estimated glomerular filtration rate (eGFR) decline in participants with normal kidney function, indicating its safety in terms of kidney function preservation.

NCBI (Pubmed)

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. Heerspink, HJL., Apperloo, E., Davies, M., et al.[2023]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11875690/

The Sit Less, Interact and Move More (SLIMM-2) Trial

Results from the SLIMM-2 study are expected to inform clinical practice, with the potential to enhance physical health and functioning among persons with CKD.

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1551714424003495

The Sit Less, Interact and Move More (SLIMM-2) Trial

The SLIMM-2 is a two-center study designed with a 3-month sedentary activity coaching (SLIMM) followed by a 9-month randomized controlled trial with three arms.

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clinicaltrials.gov

clinicaltrials.gov/study/NCT05173714

Sit Less, Interact and Move More (SLIMM) 2 Study

Prolonged sitting is associated with decreased kidney function and increased risk of diabetes, heart disease and death. In a previous pilot study funded by NIH, ...

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39608749/

The Sit Less, Interact and Move More (SLIMM-2) Trial - PubMed

Conclusions: Results from the SLIMM-2 study are expected to inform clinical practice, with the potential to enhance physical health and functioning among ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT02970123

Sit Less, Interact, Move More (SLIMM) Intervention for ...

The primary hypothesis is that the Sit Less, Interact, Move More (SLIMM) intervention in Chronic Kidney Disease (CKD) will be effective in decreasing sedentary ...

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med.stanford.edu/mosslab/research/clinicaltrial?ctid=NCT05173714&conditionId=&serviceLineId=&condition=&alpha=s

Sit Less, Interact and Move More (SLIMM) 2 Study

The purpose of this study is to see if guided resistance training (to improve muscle strength) and semaglutide (FDA approved diabetes and weight loss ...