Clinical trial NCT04907799: Daily Caloric Restriction in ADPKD
Official title: Daily Caloric Restriction in Overweight and Obese Adults With ADPKD
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Autosomal Dominant Polycystic Kidney
Overweight and Obesity
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Mayo Clinic
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2021-06-01
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This clinical trial will determine whether a daily-caloric restriction-based weight loss intervention can slow kidney growth in adults with autosomal dominant polycystic kidney disease who are overweight or obese. The study will also evaluate changes in abdominal fat by magnetic resonance imaging. Blood and fat samples will provide insight into biological changes that may contribute to any observed benefits of the intervention.

Detailed description: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by development and continued growth of numerous fluid-filled renal cysts that ultimately result in renal failure. Similar to the general population, the prevalence of overweight and obesity have been rising in ADPKD patients, effecting about two-thirds of individuals. Adipocytes do not simply act as a fat reservoir, but are active endocrine organs that promote release of pro-inflammatory cytokines, and thus, may be a promising clinical target for ADPKD management. Mounting evidence also suggests that a metabolic defect exists in ADPKD, which likely contributes to cystic epithelial proliferation and subsequent cyst growth. Additionally, the investigators recently reported that overweight and obesity are strong independent predictors of more rapid kidney growth. Collectively, these data suggest that interventions to reduce abdominal adiposity may slow ADPKD progression.

Initial results from the investigators' R03-funded pilot and feasibility study support that a 12-month daily caloric restriction (DCR)-based behavioral weight loss intervention in adults with ADPKD and overweight or obesity: 1) is feasible and acceptable; 2) slowed kidney growth (annual %∆ in height-adjusted TKV \[htTKV\]), which was highly correlated with weight loss; 3) reduced abdominal adiposity; and 4) altered pathways implicated in ADPKD progression and metabolism. These initial results suggest that a DCR-based behavioral weight loss intervention offers a promising strategy to slow ADPKD progression. However, the pilot and feasibility study was limited by a small sample size, relatively short duration, and lack of a control group. Thus, to translate these promising results of the pilot study towards clinical practice, the investigators are conducting a randomized, controlled clinical trial in a larger number of adults with ADPKD and overweight or obesity to directly compare the efficacy of a DCR-based behavioral weight loss intervention compared to control for slowing kidney growth (primary outcome) over a longer duration. Changes in abdominal adiposity will serve as a secondary outcome and effects of weight loss on circulating and adipose markers of biological pathways will provide mechanistic insight.

In a subset of participants recruited for this clinical trial, we will measure change in kidney oxidative metabolism, insulin sensitivity, plasma metabolomics, and gut microbiota. These additional measures will aim to compare kidney oxidative metabolism, insulin sensitivity, plasma metabolome and gut microbiota at baseline and 2 years. In addition, the investigators aim to define the relations among changes in kidney oxidative metabolism, insulin sensitivity, plasma metabolome, gut microbiota, total kidney volume, and body weight over 2 years. Currently, it is unknown if weight loss via DCR modifies renal energy expenditure, substrate utilization, plasma metabolomics, or the gut microbiome.

Eligibility criteria: Inclusion Criteria:

* 18-65 years of age
* ADPKD diagnosis based on the modified Pei-Ravine criteria
* Body-mass index of 25-45 kg/m\^2
* Estimated glomerular filtration rate ≥ 30 mL/min/1.73m\^2
* Total kidney volume (htTKV) \&gt; 600 mL, calculated/estimated from a previous kidney ultrasound or magnetic resonance imaging
* Access to the internet with video chat capabilities
* No plans for extended travel (\&gt;2 weeks) without internet access during the 12-month intensive period
* Not currently participating in or planning to participate in any formal weight loss or physical activity program, or another interventional study
* Ability to provide informed consent

Exclusion Criteria:

* Diabetes mellitus
* Current smokers or history of smoking in the past 12 months
* Alcohol dependence or abuse
* History of hospitalization or major surgery within the last 3 months
* Untreated dyslipidemia
* Uncontrolled hypertension
* Pregnancy, lactation, or unwillingness to use adequate birth control
* Cardiovascular disease, peripheral vascular disease, or symptoms suggestive of cardiovascular disease: chest pain, shortness of breath at rest or with mild exertion, syncope
* Abnormal resting electrocardiogram (ECG): serious arrhythmias, including multifocal premature ventricular contractions (PVC\&#39;s), frequent PVC\&#39;s (defined as 10 or more per min), ventricular tachycardia (defined as runs of 3 or more successive PVC\&#39;s), or sustained atrial tachyarrhythmia; 2nd or 3rd degree A-V block, QTc interval \&gt; 480 msec or other significant conduction defects
* Significant pulmonary disease including: chronic obstructive pulmonary disease, interstitial lung disease, cystic fibrosis, or uncontrolled asthma
* Regular use of prescription or over-the-counter medications that may affect weight, appetite, food intake, or energy metabolism unless weight stable
* History of clinically diagnosed eating disorder including: anorexia nervosa, bulimia, binge eating disorder
* Weight loss of \&gt;5% in the past 3 months for any reason except post-partum weight loss; weight gain \&gt;5% requires assessment by PI
* Major psychiatric disorder (e.g., psychosis, schizophrenia, mania, bipolar disorder) or current severe depression, based on DSM-IV-TR criteria for Major Depressive Episode, which in the opinion of the Study MD would interfere with ability to adhere to dietary interventions)
* Inability to cooperate with or clinical contraindication for magnetic resonance imaging, including: severe claustrophobia, implants, devices, or non-removable body piercings
* Previous obesity treatment with surgery or weight loss device, except: (1) liposuction and/or abdominoplasty if performed \&gt; 1 year before screening, (2) lap banding if the band has been removed \&gt; 1 year before screening, (3) intragastric balloon if the balloon has been removed \&gt; 1 year before screening (4) duodenal-jejunal bypass sleeve, if the sleeve has been removed \&gt; 1 year before screening or 5) AspireAssist or other endoscopically placed weight loss device if the device has been removed \&gt; 1 year before screening.

Primary outcomes:
measure: Change in height-Adjusted Total kidney volume
timeFrame: Baseline, 24-months
Secondary outcomes:
measure: Change in abdominal adiposity
timeFrame: Baseline, 24-months
measure: Change in the ratio of insulin-like growth factor-1 (IGF-1)/ to GF binding protein-1
timeFrame: Baseline, 12-months, 24-months
measure: Change in adiponectin (circulating)
timeFrame: Baseline, 12-months, 24-months
measure: Change in leptin (circulating)
timeFrame: Baseline, 12-months, 24-months
measure: Change in interleukin-6 (circulating)
timeFrame: Baseline, 12-months, 24-months
measure: Change in tumor necrosis factor-alpha (circulating)
timeFrame: Baseline, 12-months, 24-months
measure: Change in C-reactive protein (circulating)
timeFrame: Baseline, 12-months, 24-months
measure: Change in peripheral blood mononuclear cell protein expression of pAMPK/AMPK
timeFrame: Baseline, 12-months, 24-months
measure: Change in peripheral blood mononuclear cell protein expression of pS6K/S6K
timeFrame: Baseline, 12-months, 24-months
measure: Change in adiponectin (adipose tissue)
timeFrame: Baseline, 24-months
measure: Change in leptin (adipose tissue)
timeFrame: Baseline, 24-months
measure: Change in interleukin-6 (adipose tissue)
timeFrame: Baseline, 24-months
measure: Change in tumor necrosis factor-alpha (adipose tissue)
timeFrame: Baseline, 24-months
measure: Change in renal oxygen consumption
timeFrame: Baseline, 24-months
measure: Change in gut microbiota
timeFrame: Baseline, 24-months
measure: Change in plasma metabolome
timeFrame: Baseline, 24-months
Other outcomes:
measure: Safety (adverse events)
timeFrame: 24-months
measure: Change in dietary Energy Intake
timeFrame: Baseline, 1-, 6-, 12-, and 24-months
measure: Adherence
timeFrame: 24 months
measure: Tolerability (dropout due to adverse events)
timeFrame: 24 months
measure: Change in free-living physical activity
timeFrame: Baseline, 6-, 12- and 24-months
measure: Change in percent body fat
timeFrame: Baseline, 24-months
measure: Change in plasma choline
timeFrame: Baseline, 24-months
measure: Change in plasma trimethylamine
timeFrame: Baseline, 24-months
measure: Change in plasma trimethylamine-N-oxide
timeFrame: Baseline, 24-months
Locations:
city: Aurora
country: United States
facility: University of Colorado - Anschutz Medical Campus
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Kristen Nowak, PhD, MPH
role: PRINCIPAL_INVESTIGATOR
References: