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

February 8, 2022 updated by: University of Colorado, Denver
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.

Study Overview

Status

Completed

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Colorado
      • Aurora, Colorado, United States, 80045
        • Kristen Nowak

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Weight loss behavioral intervention via one of two strategies.
Experimental: 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).
Weight loss behavioral intervention via one of two strategies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility to Enroll and Retain Participants
Time Frame: Through study completion, an expected duration of 18 months
Numbers of individuals pre-screened
Through study completion, an expected duration of 18 months
Feasibility to Enroll Participants
Time Frame: Through study completion, an expected duration of 18 months
Numbers of individuals screened
Through study completion, an expected duration of 18 months
Feasibility to Retain Participants
Time Frame: Through study completion, an expected duration of 18 months
Numbers of individuals enrolled
Through study completion, an expected duration of 18 months
Feasibility to Retain Participants
Time Frame: Through study completion, an expected duration of 18 months
Numbers of individuals retained
Through study completion, an expected duration of 18 months
Percent Change From Baseline Body Weight (Weight Loss)
Time Frame: Baseline, 12 weeks, and 1 year
Measurement of body weight pre to post intervention in each group
Baseline, 12 weeks, and 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Tolerability, Measured as Adverse Events
Time Frame: 1 year
Number of participants with treatment-related adverse events in each group as evaluated by monthly phone questionnaire
1 year
Quality of Life Scores at Baseline
Time Frame: Baseline
Quality of life (QOL) will be assessed with the RAND 36 Item Health Survey (RAND-36) physical and mental health component summary score. The Rand-36 measures quality of life. Possible scores for each subscale range from 0 to 100, with higher scores indicating a better quality of life and better outcome.
Baseline
Quality of Life Scores at 12 Weeks
Time Frame: 12 Weeks
Quality of life (QOL) will be assessed with the RAND 36 Item Health Survey (RAND-36) physical and mental health component summary score. The Rand-36 measures quality of life. Possible scores for each subscale range from 0 to 100, with higher scores indicating a better quality of life and better outcome.
12 Weeks
Quality of Life Scores at 1 Year
Time Frame: 1 Year
Quality of life (QOL) will be assessed with the RAND 36 Item Health Survey (RAND-36) physical and mental health component summary score. The Rand-36 measures quality of life. Possible scores for each subscale range from 0 to 100, with higher scores indicating a better quality of life and better outcome.
1 Year
Mood at Baseline
Time Frame: Baseline
Mood state will be assessed with the Profile of Mood States 2 (POMS-2). The POMS-2 measures mood. Possible scores for the Vigor scale range from 0 to 32, with higher scores for indicating a better outcome. Possible scores for the fatigue scale range from 0 to 28 with higher scores indicating a worse outcome.
Baseline
Mood at 12 Weeks
Time Frame: 12 Weeks
Mood state will be assessed with the Profile of Mood States 2 (POMS-2). The POMS-2 measures mood. Possible scores range from 0 to 20 for both the Vigor and Fatigue subscales, with higher scores indicating a worse outcome.
12 Weeks
Mood at 1 Year
Time Frame: 1 Year
Mood state will be assessed with the Profile of Mood States 2 (POMS-2). The POMS-2 measures mood. Possible scores range from 0 to 20 for both the Vigor and Fatigue subscales, with higher scores indicating a worse outcome.
1 Year
Change in Energy Intake
Time Frame: Baseline, 12 weeks and 1 year
Self-reported energy intake
Baseline, 12 weeks and 1 year
Change in Macronutrient Intake
Time Frame: Baseline, 12 weeks and 1 year
Self-reported macronutrient intake
Baseline, 12 weeks and 1 year
Serum Insulin-like Growth Factor-1 Levels at Baseline
Time Frame: Baseline
Serum insulin-like growth factor-1 (IGF-1) levels will be evaluated in each group
Baseline
Serum Insulin-like Growth Factor-1 Levels at 12 Weeks
Time Frame: 12 Weeks
Serum insulin-like growth factor-1 (IGF-1) levels will be evaluated in each group
12 Weeks
Serum Insulin-like Growth Factor-1 Levels at 1 Year
Time Frame: 1 Year
Serum insulin-like growth factor-1 (IGF-1) levels will be evaluated in each group
1 Year
Insulin-like Growth Factor Binding Protein-1 Levels at Baseline
Time Frame: Baseline
Insulin-like growth factor binding protein-1 (IGFBP-1) levels will be evaluated in each group
Baseline
Insulin-like Growth Factor Binding Protein-1 Levels at 12 Weeks
Time Frame: 12 Weeks
Insulin-like growth factor binding protein-1 (IGFBP-1) levels will be evaluated in each group
12 Weeks
Insulin-like Growth Factor Binding Protein-1 Levels at 1 Year
Time Frame: 1 Year
Insulin-like growth factor binding protein-1 (IGFBP-1) levels will be evaluated in each group
1 Year
Change in PBMC Ratio of pS6K/s6K
Time Frame: Baseline and 1 year
Ratio of protein expression of phosphorylated S6K to S6K peripheral blood mononuclear cell protein expression of S6 kinase (S6K) in each group.
Baseline and 1 year
Change in PBMC pAMPK/AMPK Expression
Time Frame: Baseline and 1 year
Ratio of peripheral blood mononuclear cell protein expression of phosphorylated AMP-activated kinase (AMPK) to AMPK in each group
Baseline and 1 year
Percent Change in Total Kidney Volume by Magnetic Resonance Imaging (MRI)
Time Frame: Baseline and 1 year
Percent change from baseline in height adjusted total kidney volume by MRI in each group
Baseline and 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Kristen Nowak, Ph.D., MPH, University of Colorado - Anschutz Medical Campus

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 4, 2018

Primary Completion (Actual)

October 13, 2020

Study Completion (Actual)

October 13, 2020

Study Registration Dates

First Submitted

October 27, 2017

First Submitted That Met QC Criteria

November 13, 2017

First Posted (Actual)

November 17, 2017

Study Record Updates

Last Update Posted (Actual)

March 3, 2022

Last Update Submitted That Met QC Criteria

February 8, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

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.

IPD Sharing Time Frame

Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.

IPD Sharing Access Criteria

Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA).

IPD Sharing Supporting Information Type

  • Study Protocol
  • Informed Consent Form (ICF)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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