Caloric Restriction for Polycystic Kidney Disease

(EXPLORE Trial)

Overseen By Kristen Nowak, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Colorado, Denver

Must not be taking: Weight loss drugs

Disqualifiers: Diabetes, Smoking, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the impact of a 2-year daily caloric restriction on kidney health and insulin sensitivity in individuals with autosomal dominant polycystic kidney disease (ADPKD) who are overweight or obese. Participants will follow a diet plan to reduce calorie intake by 30% while increasing physical activity. Eligible participants must have an ADPKD diagnosis, be overweight, and have internet access for video chats. The trial will compare two groups: one following the diet plan and another receiving standard dietary advice. As an unphased trial, it offers participants a unique opportunity to contribute to understanding lifestyle interventions in ADPKD.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you must stop taking your current medications. However, if you regularly use medications that affect weight, appetite, food intake, or energy metabolism, you may be excluded from participating.

What prior data suggests that daily caloric restriction is safe for individuals with polycystic kidney disease?

Research has shown that reducing daily calorie intake by about 30% is a common and safe method for weight loss in people with obesity. In studies involving patients with autosomal dominant polycystic kidney disease (ADPKD), this approach led to significant weight loss.

These studies found no major safety issues, suggesting that this diet is generally safe for individuals with ADPKD. Participants successfully adhered to the diet, indicating its manageability for most people.

While no treatment is entirely risk-free, current research supports the safety of this approach for individuals with ADPKD who are overweight or obese. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the potential of daily caloric restriction for treating polycystic kidney disease (PKD) because it offers a unique, non-pharmacological approach. Unlike the standard treatments, which often involve medications to manage symptoms or slow disease progression, this method focuses on a significant lifestyle change — reducing daily caloric intake by 30% and increasing physical activity. This approach could not only help in managing PKD but also improve overall health and wellness, making it an appealing option for patients seeking alternatives to medication.

What evidence suggests that daily caloric restriction might be an effective treatment for polycystic kidney disease?

This trial will compare the effects of daily caloric restriction with standard advice for managing polycystic kidney disease (ADPKD). Research has shown that reducing daily calorie intake might benefit people with ADPKD. Studies suggest that cutting calories can slow kidney cyst growth and improve kidney health. This approach may also enhance overall health, which is crucial for those with ADPKD. Early findings indicate that eating less could slow the disease's progression. Overall, reducing calorie intake appears promising for managing ADPKD. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for overweight or obese adults aged 18-65 with autosomal dominant polycystic kidney disease (ADPKD) and a body-mass index of 25-45 kg/m^2. Participants must have internet access, not be in other weight loss programs, and have a certain level of kidney function. Exclusions include serious heart conditions, recent significant weight changes, diabetes, substance abuse issues, major psychiatric disorders, inability to undergo MRI scans, smoking history within the past year.

Inclusion Criteria

Ability to provide informed consent

Not currently participating in or planning to participate in any formal weight loss or physical activity program, or another interventional study

Access to the internet with video chat capabilities

Exclusion Criteria

My heart's rhythm is irregular or I have a serious heart condition.

I have lost more than 5% of my weight in the last 3 months, not due to childbirth.

Alcohol dependence or abuse

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments including PET/CT scan and hyperinsulinemic-euglycemic clamp

1-2 weeks

1 visit (in-person)

Treatment

Participants in the caloric restriction group undergo a 2-year behavioral weight loss intervention

24 months

Regular group sessions (frequency not specified)

Follow-up

Participants are monitored for changes in renal oxygen consumption and insulin sensitivity

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Daily Caloric Restriction

Trial Overview The study tests how daily caloric restriction over two years affects kidney oxidative metabolism and insulin sensitivity in ADPKD patients compared to standard advice control. It's designed as a pilot study where participants are given specific dietary interventions to follow.

How Is the Trial Designed?

Group I: Other: Standard Advice Control Experimental Treatment 1 Intervention

The standard advice control group will receive an initial consultation with a registered dietician regarding current clinical recommendations for ADPKD without subsequent counseling sessions.

Group II: Daily Caloric Restriction Experimental Treatment 1 Intervention

The daily caloric restriction group will participate in a 2-year, group-based, behavioral weight loss intervention based on a 30% reduction in caloric intake and increased physical activity.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Nutrition Obesity Research Center

Collaborator

Trials

5

Recruited

120+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Nutrition Obesity Research Center

Collaborator

Trials

7

Recruited

240+

Published Research Related to This Trial

Chronic renal failure (CRF) patients can maintain a neutral nitrogen balance similar to healthy individuals even with restricted protein intake, suggesting that low-protein diets (LPDs) can be effective in managing their condition.

LPDs can help alleviate symptoms of uremia and slow the progression of renal failure, but patients need to be monitored for dietary compliance and nutritional adequacy to ensure their health is maintained.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein restriction and malnutrition in renal disease: fact or fiction? Maroni, BJ.[2007]

A modified low-calorie diet using meal replacements was found to be safe and effective for weight loss in five hemodialysis patients over a median duration of 364 days, with participants losing an average of 7% of their body weight.

The diet resulted in significant energy deficits and no major safety concerns were reported, suggesting that meal replacements can be a viable strategy for weight management in patients preparing for kidney transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meal replacements as a strategy for weight loss in obese hemodialysis patients. Lassemillante, AM., Oliver, V., Hickman, I., et al.[2018]

In a study of Han:SPRD-cy rats, a low-protein diet (8% casein) significantly reduced tubular epithelial remodeling and interstitial pathology compared to a normal-protein diet (20% casein), indicating that dietary protein restriction can slow the progression of polycystic kidney disease.

The low-protein diet led to notable decreases in interstitial fibrosis, cellularity, and macrophage infiltration, suggesting that it effectively reduces inflammation and tissue damage in the kidneys of these rats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal remodelling in dietary protein modified rat polycystic kidney disease. Bankovic-Calic, N., Eddy, A., Sareen, S., et al.[2006]

In a study of 131 patients with autosomal dominant polycystic kidney disease (ADPKD) who used ketogenic dietary interventions (KDIs), 86% reported overall health improvements and 67% noted benefits related to ADPKD symptoms, suggesting potential efficacy of KDIs.

The study indicated that KDIs were generally safe and feasible, with 90% of participants experiencing significant weight loss and 64% reporting improvements in hypertension, although some adverse effects were noted, highlighting the need for further controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic dietary interventions in autosomal dominant polycystic kidney disease-a retrospective case series study: first insights into feasibility, safety and effects. Strubl, S., Oehm, S., Torres, JA., et al.[2023]

Recent evidence suggests that specific dietary regimens, such as caloric restriction, intermittent fasting, and ketogenic diets, may help slow the progression of autosomal dominant polycystic kidney disease (ADPKD) by influencing nutrient signaling in the kidneys.

The review highlights the potential for these dietary interventions to not only impact kidney health but also provide systemic metabolic benefits, with ongoing human clinical trials expected to provide further insights.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary Interventions in Autosomal Dominant Polycystic Kidney Disease. Pickel, L., Iliuta, IA., Scholey, J., et al.[2023]

In a study of 51 patients with chronic renal insufficiency, alternating between low and high protein diets over 4-week periods led to a significant increase in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), indicating potential benefits of dietary protein variation.

The increase in GFR was particularly notable in patients with chronic glomerulonephritis, suggesting that protein restriction may be more effective in certain types of kidney disease, although the exact mechanism behind these changes remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of changes in daily protein intake on renal function in chronic renal insufficiency: differences in reaction according to disease entity. Schaap, GH., Bilo, HJ., van der Meulen, J., et al.[2018]

In a study analyzing 28 daily menus for patients on low-protein diets (LPDs) for chronic renal failure, it was found that most diets (7 out of 9) did not provide sufficient energy, lacking about 500 kcal/day.

Protein-calorie malnutrition (PCMN) in these patients is often due to inadequate energy intake rather than just protein restriction, suggesting that caloric supplements and proper dietary counseling are essential for preventing malnutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caloric supplements for patients on low-protein diets? Gretz, N., Lasserre, J., Strauch, M.[2018]

Food restriction (FR) in mouse models of autosomal dominant polycystic kidney disease (ADPKD) significantly slows disease progression by reducing cyst area, renal fibrosis, inflammation, and injury in a dose-dependent manner.

The beneficial effects of FR are linked to the suppression of the mTOR pathway and activation of the LKB1/AMPK pathway, suggesting that dietary interventions could be a novel therapeutic approach for managing ADPKD in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Food Restriction Ameliorates the Development of Polycystic Kidney Disease. Warner, G., Hein, KZ., Nin, V., et al.[2018]

Daily caloric restriction (DCR) and intermittent fasting (IMF) were both feasible for overweight or obese patients with autosomal dominant polycystic kidney disease (ADPKD), with DCR leading to greater weight loss and better adherence.

In a mouse model of ADPKD, only DCR resulted in significant weight loss and slowed cyst growth, suggesting that caloric restriction may be an effective therapeutic strategy for managing ADPKD progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss and cystic disease progression in autosomal dominant polycystic kidney disease. Hopp, K., Catenacci, VA., Dwivedi, N., et al.[2023]

Nutritional modifications and monitoring are crucial for patients with chronic kidney disease (CKD) as they can significantly impact health outcomes, including the progression to kidney failure and overall quality of life.

Dietary interventions are essential in managing non-dialysis CKD (ND-CKD) stages 3-5, as they can help prevent complications like overweight and protein energy-wasting, highlighting the importance of diet in kidney health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing Diet to Slow CKD Progression. Molina, P., Gavela, E., Vizcaíno, B., et al.[2021]

Dietary protein restriction has been shown to significantly slow the progression of chronic renal insufficiency, which is crucial for patients with end-stage renal disease, a condition that leads to high morbidity and healthcare costs.

The review highlights the need for further research to address remaining questions about the optimal levels and methods of protein restriction in managing chronic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-protein diets in renal disease. Zeller, KR.[2019]

In a study of 169 patients with chronic renal failure, a low-protein diet was well tolerated and did not lead to malnutrition, maintaining stable serum albumin and prealbumin levels over a year.

While both diabetic and nondiabetic patients experienced weight loss and reduced obesity indices, only nondiabetic patients showed a significant slowing of renal function decline when on a low-protein diet, suggesting dietary protein restriction may be beneficial for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adequate protein dietary restriction in diabetic and nondiabetic patients with chronic renal failure. Meloni, C., Tatangelo, P., Cipriani, S., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04907799

NCT04907799 | Daily Caloric Restriction in ADPKD This clinical trial will determine whether a daily-caloric restriction-based weight loss intervention can slow kidney growth in adults with autosomal ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11976525/

Time-restricted eating and autosomal dominant polycystic ... Time-restricted eating (TRE) is a fasting regimen that restricts eating to a particular window (typically 8 hours/day), which could slow cyst growth based on ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03342742

Study Details | NCT03342742 | Daily Caloric Restriction ... Collectively, these data suggest that dietary restriction regimens may slow ADPKD progression. Accordingly, the primary aim is to determine the feasibility of ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11108253/

Polycystic Kidney Disease Diet: What is Known and ... Dietary interventions such as caloric restriction, intermittent fasting, and ketogenic diet hold promise in ADPKD management by enhancing metabolic health.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2161831322000825

Dietary Interventions in Autosomal Dominant Polycystic ... More tightly specified dietary regimens, including caloric restriction, intermittent fasting, and ketogenic diets, hold promise to slow disease progression.

6. pkdcure.org pkdcure.org/resources/adpkd-weight-loss-study-findings/

ADPKD Weight Loss Study Findings The major takeaway from this work is that both dietary interventions are feasible and result in clinically significant weight loss. Additionally ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2589004221016679

Weight loss and cystic disease progression in autosomal ... We demonstrate the feasibility of daily caloric restriction (DCR) and intermittent fasting (IMF) in a cohort of overweight or obese patients with ADPKD.