An interventional study of Dietary in Polycystic Kidney, Autosomal Dominant, sponsored by University of Colorado, Denver. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2023-04-10.
Sponsored by University of Colorado, Denver · Not applicable, Interventional, and Other
The proposed research will determine the feasibility of a time restricted feeding intervention,a fasting regimen that restricts eating to a feeding window (8 hrs/day) for 1 year in adults with autosomal dominant polycystic kidney disease (ADPKD) who are overweight or obese. The study will provide valuable information on the intervention in terms of safety, adherence, acceptability, and tolerability. Last, this pilot trial will provide initial insight into biological changes including abdominal adiposity, changes in kidney growth and function, and markers of biological pathways related to the intervention.
Mounting evidence suggests that a metabolic defect exists in autosomal dominant polycystic kidney disease (ADPKD), which likely contributes to cystic epithelial proliferation and subsequent cyst growth. There are notable overlapping features and pathways among metabolism, obesity, and/or ADPKD. The investigators recently reported that in the Halt Progression of Polycystic Kidney Disease (HALT-PKD) Study A that overweight and obesity are strong independent predictors of more rapid kidney growth. Moving beyond body mass index, the investigators have novel preliminary data using magnetic resonance images (MRIs) from a small number of participants from HALT-PKD Study A that abdominal adiposity is an independent predictor of kidney growth and kidney function decline. Adipocytes do not simply act as a fat reservoir but are active endocrine organs that promote release of pro-inflammatory cytokines and produce adipokines. Numerous signaling pathways promoted by adipocytes are also implicated in cystogenesis. Periods of fasting may counter adiposity-mediated signaling pathways and slow ADPKD progression. Mild-to-moderate food restriction profoundly slows cyst growth and maintains renal function in rodent models of ADPKD, which are characterized by metabolic reprogramming favoring enhanced aerobic glycolysis. Notably, fasting promotes a shift from carbohydrate to fat metabolism, which could suppress cyst growth. The investigators are currently conducting an ongoing behavioral weight loss pilot trial (based on either daily caloric restriction or intermittent fasting) in adults with ADPKD who are overweight/obese. As an alternative to these approaches, time-restricted feeding (TRF) is a novel fasting regimen that restricts eating to a feeding window (typically 8-12 hrs/day). As isocaloric TRF reduces disease progression in a rodent model of ADPKD, including kidney: body weight and mammalian target of rapamycin (mTOR) activity, it may be an alternative and easier to adhere to dietary strategy to slow ADPKD progression. Specific Aim: Determine the feasibility of TRF without energy intake restriction in adults with ADPKD and overweight/obesity. The study will determine adherence to TRF by assessing the percent of participants achieving the goal of eating within an 8-hour TRF window, measured objectively with a photographic food record and verified with continuous glucose monitoring data. The study will also further assess the safety, acceptability, and tolerability of TRF by evaluation of safety labs, adverse events, and quality of life measures, as well as changes in abdominal adiposity and total kidney volume (TKV) by magnetic resonance imaging (MRI), and markers of biological pathways (AMP-activated protein kinase [AMPK], mTOR, insulin-like growth factor 1 [IGF1]).
Exclusion Criteria:
Instructed to eat within an 8-hr window, beginning within 3 hrs of waking. In addition, provide current clinical recommendations for the management of ADPKD, as well as chronic kidney disease, including moderate dietary sodium restriction (2.3-3 g), appropriate hydration, protein intake of 0.8/1.0 g/kg ideal body weight, moderate daily phosphate restriction (800 mg), and moderation in caloric intake.
Behavioral: Dietary
Curriculum for the healthy eating control group will emphasize current clinical recommendations for the management of ADPKD, as well as chronic kidney disease, including moderate dietary sodium restriction (2.3-3 g), appropriate hydration, protein intake of 0.8/1.0 g/kg ideal body weight, moderate daily phosphate restriction (800 mg), and moderation in caloric intake.
Behavioral: Dietary
Dietary intake behavioral intervention via time restricted feeding and normal healthy eating recommendations vs. normal healthy eating recommendations without restricted
Adherence
Percent adherence to the 8-hr TRF window (during the 7 day recordng period)
Time frame: 1 year
Feasibility to enroll participants
Numbers of individuals pre-screened and enrolled
Time frame: Through study enrollment, an expected duration of 12 months
Feasibility to retain participants
Numbers of individuals retained
Time frame: Through study completion, an expected duration of 24 months
Safety and tolerability, measured as adverse events
Number of participants with treatment-related adverse events in each group as evaluated by the Safety Officer
Time frame: Through study completion, an expected duration of 24 months
Change in Body Weight
Body weight will be measured at baseline and monthly, using BodyTrace scales for remote, secure transmission of data.
Time frame: 1 year
Change in Abdominal adiposity
Abdominal adiposity will be quantified using MRI
Time frame: 1 year
Change in Body Composition
Body composition measured via dual-energy X-ray absorptiometry (DEXA)
Time frame: 1 year
Change in insulin-like growth factor binding protein-1 levels
Fasting serum insulin-like growth factor binding protein-1 (IGFBP-1) levels will be evaluated in each group
Time frame: 1 year
Change in serum insulin-like growth factor-1 levels
Fasting serum insulin-like growth factor-1 (IGF-1) levels will be evaluated in each group
Time frame: 1 year
Change in peripheral blood mononuclear cell (PBMC) AMPK expression
Peripheral blood mononuclear cell protein expression of AMP-activated kinase (AMPK) in each group
Time frame: 1 year
Change in PBMC S6K expression
Peripheral blood mononuclear cell protein expression of S6 kinase (S6K) in each group
Time frame: 1 year
Change in β-hydroxybutyrate levels
Serum β-hydroxybutyrate levels in each group
Time frame: 1 year
Change in total kidney volume by magnetic resonance imaging (MRI)
Change in total kidney volume by MRI in each group
Time frame: 1 year
Change in quality of life
Quality of life (QOL) will be assessed with the RAND 36 Item Health Survey (RAND-36) physical and mental health component summary score
Time frame: 1 year
Change in mood
Mood state will be assessed with the Profile of Mood States 2 (POMS-2)
Time frame: 1 year
Change in pain
Modified version of the Wisconsin Brief Pain Survey
Time frame: 1 year
Change in resting energy expenditure
Standard indirect calorimetry
Time frame: 1 year
Change in energy intake
24-hr dietary recalls will be analyzed using a random day in the 7-day photographic food record/continuous glucose monitoring collection period to evaluate self-reported energy intake
Time frame: 1 year
Change in macronutrient intake
24-hr dietary recalls will be analyzed using a random day in the 7-day photographic food record/CGM collection period to evaluate self-reported energy intake
Time frame: 1 year
Change in self-reported physical activity
Self-reported physical activity will be quantified using the Stanford Physical Activity Questionnaire
Time frame: 1 year
Plan to share: Yes — Data obtained through this study may be provided to qualified researchers with academic interest in ADPKD. Data shared will be coded, with no PHI included. Approval of the request and execution of all applicable agreements (i.e. data use agreement) are prerequisites to the sharing of data with the requesting party.
Supporting information: Study protocol, Icf
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University of Colorado, Denver