Daily Caloric Restriction and Intermittent Fasting in Overweight and Obese Adults With Autosomal Dominant Polycystic Kidney Disease

NCT ID: NCT03342742

Last Updated: 2022-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-04
• Study Completion Date: 2020-10-13

Brief Summary

The proposed research will determine the feasibility of delivering two behavioral weight loss interventions for 1 year in adults with autosomal dominant polycystic kidney disease (ADPKD) who are overweight or obese. The study will also compare these two interventions in terms of safety, acceptability, and tolerability. Last, this pilot trial will provide initial insight into a) biological changes and b) changes in kidney growth with each of the two weight loss interventions.

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. Surprisingly, the role of obesity in ADPKD progression is currently unknown. The investigators have novel preliminary data that overweight and obesity are independently associated with substantially faster kidney growth in ADPKD patients. Furthermore, in rodent models of ADPKD, mild-to-moderate food restriction profoundly slows cyst growth and maintains renal function via mechanisms including AMPK-activated kinase pathway activation and suppression of mammalian target of rapamycin/S6 kinase signaling and insulin-like growth factor-1 levels. Collectively, these data suggest that dietary restriction regimens may slow ADPKD progression. Accordingly, the primary aim is to determine the feasibility of delivering a 1 year behavioral weight loss intervention program in 30 overweight/obese adults with ADPKD, based on either daily caloric restriction (DCR) or intermittent fasting (IMF), with a similar (~34%) targeted weekly energy deficit. A key secondary goal is to evaluate safety, acceptability, and tolerability of IMF in ADPKD versus DCR. Last, the third exploratory aim is to a) obtain mechanistic insight into biological pathways that may be altered and b) provide initial insight into any changes in total kidney volume by magnetic resonance imaging with IMF and/or DCR.

Conditions

Polycystic Kidney, Autosomal Dominant

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Daily Caloric Restriction

The daily caloric restriction group will be instructed to reduce energy intake by a 34% daily energy deficit from baseline individual weight maintenance energy requirements.

Group Type: EXPERIMENTAL

Weight Loss

Intervention Type: BEHAVIORAL

Weight loss behavioral intervention via one of two strategies.

Intermittent Fasting

Participants in the intermittent fasting group will be instructed to reduce energy intake to \~20% of estimated energy requirement (delivered as a single meal) three non-consecutive days per week, resulting in a weekly energy deficit of \~34% (similar to the daily caloric restriction group).

Group Type: EXPERIMENTAL

Weight Loss

Intervention Type: BEHAVIORAL

Weight loss behavioral intervention via one of two strategies.

Interventions

Weight Loss

Weight loss behavioral intervention via one of two strategies.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

1. Aged 18-65 years

2. ADPKD diagnosis based on the modified Pei-Ravine criteria

3. BMI 25-45 kg/m^2

4. Normal to mildly declined renal function with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 by the CKD-EPI equation

5. Access to the internet with video chat capabilities

6. No plans for extended travel (>2 weeks) during the 3 month intesive period

7. Not currently participating in another interventional study or weight loss program

8. Ability to provide informed consent

Exclusion Criteria

1. Diabetes mellitus (diagnosis or fasting glucose >126 mg/dL or Hemoglobin A1C >6.5%)

2. Current nicotine use or history of use in the past 12 months

3. Alcohol or substance abuse (self-report or undergoing treatment)

4. History of hospitalization or major surgery within the last 3 months

5. Untreated dyslipidemia (low density lipoprotein cholesterol > 190 mg/dL or triglycerides >400 mg/dL)

6. Uncontrolled hypertension (systolic blood pressure > 160 or diastolic blood pressure >100 mm Hg)

7. Pregnancy, lactation, or unwillingness to use adequate birth control

8. Cardiovascular disease, peripheral vascular disease, cerebrovascular disease, significant pulmonary or gastrointestinal disease (described below), cancer (within the last 5 years, except skin cancer or other cancers considered cured with excellent prognosis)

9. Abnormal resting electrocardiogram (ECG): serious arrhythmias, including multifocal PVC's, frequent PVC's (defined as 10 or more per min), ventricular tachycardia (defined as runs of 3 or more successive PVC's), or sustained atrial tachyarrhythmia; 2nd or 3rd degree A-V block, QTc interval > 480 msec or other significant conduction defects

10. Significant gastrointestinal disorders including: chronic malabsorptive conditions, peptic ulcer disease, Crohn's disease, ulcerative colitis, chronic diarrhea, or active gallbladder disease

11. Significant pulmonary disorders including: chronic obstructive pulmonary disease, interstitial lung disease, cystic fibrosis, or uncontrolled asthma

12. Regular use of prescription or over-the-counter medications that may affect weight, appetite, food intake, or energy metabolism (e.g. appetite suppressants, lithium, stimulants, anti-psychotics, tricyclic antidepressants; Study M.D. will be consulted as needed; antibiotics started during the intervention period are not an exclusion); regular use of obesity pharmacotherapeutic agents within the last 6 month

13. History of clinically diagnosed eating disorder including anorexia nervosa, bulimia, binge eating disorder

14. Weight loss >5% in past 3 months for any reason except post-partum weight loss; weight gain >5% in past 3 months requires assessment by PI to determine reason for weight gain and if it is appropriate for the subject to participate in the study.

15. Untreated hyper- or hyperthyroidism (TSH outside of normal range for laboratory or history of uncontrolled thyroid disorder). History of thyroid disorder or current thyroid disease treated with stable medication regimen for at least 6 months in acceptable.

16. Current severe depression or history of severe depression within the previous year, based on DSM-IV-TR criteria for Major Depressive Episode.

17. History of other significant psychiatric illness (e.g. psychosis, schizophrenia, mania, bipolar disorder) which in the opinion of the Study MD would interfere with ability to adhere to dietary interventions.

18. Inability to cooperate with/clinical contraindication for MRI including severe claustrophobia, implants, devices, or non-removable body piercings

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kristen Nowak, Ph.D., MPH

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

Kristen Nowak

Aurora, Colorado, United States

Countries

United States

References

St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

Reference Type: DERIVED

PMID: 39356039 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R03DK118215

Identifier Type: NIH

Identifier Source: secondary_id

View Link

17-1327

Identifier Type: -

Identifier Source: org_study_id