Time Restricted Feeding in Autosomal Dominant Polycystic Kidney Disease
Condition: Polycystic Kidney, Autosomal Dominant
MeSH terms: Arthrogryposis; Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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]).
    

Intervention name(s): Dietary
Intervention type(s): Behavioral
Intervention description(s): Dietary intake behavioral intervention via time restricted feeding and normal healthy eating recommendations vs. normal healthy eating recommendations without restricted
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Timed Feeding; Kidney Diseases; Body Weight