Caloric Restriction for Polycystic Kidney Disease

(EXPLORE Trial)

Recruiting in Aurora (>99 mi)

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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The proposed research is a pilot study assessing kidney oxidative metabolism and insulin sensitivity after a 2-year weight loss intervention in those with autosomal dominant polycystic kidney disease who are overweight or obese.

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 data supports the idea that Caloric Restriction for Polycystic Kidney Disease is an effective treatment?

The available research does not provide specific data supporting the effectiveness of Caloric Restriction for Polycystic Kidney Disease. Instead, it focuses on protein restriction and its effects on chronic kidney conditions. One study mentions that protein restriction has less effect on adult polycystic kidney disease compared to other kidney diseases. Another study highlights the risk of malnutrition with low-protein diets, suggesting that caloric supplements might be necessary. Overall, the research does not directly support Caloric Restriction as an effective treatment for Polycystic Kidney Disease. ^{1 2 3 4 5}

What safety data exists for caloric restriction in treating polycystic kidney disease?

The safety data for caloric restriction in treating polycystic kidney disease (PKD) is primarily derived from studies on dietary interventions in animal models and human case series. Food restriction has been shown to slow disease progression in mouse models of PKD, with no specific safety concerns reported. A retrospective case series study on ketogenic dietary interventions in PKD patients suggests feasibility and safety, though detailed safety outcomes are not specified. In a study involving overweight or obese PKD patients, daily caloric restriction (DCR) was found to be more effective and better tolerated than intermittent fasting, with no major safety issues reported. Additionally, a study on meal replacements in hemodialysis patients, which included caloric restriction, found the approach to be safe and effective for weight loss, with no significant safety concerns noted. Overall, while these studies suggest that caloric restriction can be safe, more comprehensive clinical trials are needed to fully establish its safety profile in PKD patients. ^{6 7 8 9 10}

Is daily caloric restriction a promising treatment for polycystic kidney disease?

Yes, daily caloric restriction is promising because it can lead to significant weight loss and slow the growth of kidney cysts, which may help manage polycystic kidney disease. ^{1 6 8 11 12}

Eligibility Criteria

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

My kidney function is adequate.

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.

I have diabetes.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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 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]

References

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

Adequate protein dietary restriction in diabetic and nondiabetic patients with chronic renal failure. [2022]

2. Switzerland 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. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Caloric supplements for patients on low-protein diets? [2018]

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

Optimizing Diet to Slow CKD Progression. [2021]

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

Low-protein diets in renal disease. [2019]

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

Food Restriction Ameliorates the Development of Polycystic Kidney Disease. [2018]

7. England 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. [2023]

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

Weight loss and cystic disease progression in autosomal dominant polycystic kidney disease. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Protein restriction and malnutrition in renal disease: fact or fiction? [2007]

10. Canada pubmed.ncbi.nlm.nih.gov

Meal replacements as a strategy for weight loss in obese hemodialysis patients. [2018]

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

Dietary Interventions in Autosomal Dominant Polycystic Kidney Disease. [2023]

12. Germany pubmed.ncbi.nlm.nih.gov

Renal remodelling in dietary protein modified rat polycystic kidney disease. [2006]