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

Polycystic Kidney, Autosomal Dominant Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03342742
• Other study ID #: 17-1327
• Secondary ID: R03DK118215
• Status: Completed
• Phase: N/A
• Start date: June 4, 2018
• Est. completion date: October 13, 2020

Study information

• Verified date: February 2022
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: October 13, 2020
• Est. primary completion date: October 13, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Arthrogryposis
• Kidney Diseases
• Overweight
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Intervention

Behavioral:
• Weight Loss
Weight loss behavioral intervention via one of two strategies.

Locations

Country	Name	City	State
United States	Kristen Nowak	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility to Enroll and Retain Participants	Numbers of individuals pre-screened	Through study completion, an expected duration of 18 months
Primary	Feasibility to Enroll Participants	Numbers of individuals screened	Through study completion, an expected duration of 18 months
Primary	Feasibility to Retain Participants	Numbers of individuals enrolled	Through study completion, an expected duration of 18 months
Primary	Feasibility to Retain Participants	Numbers of individuals retained	Through study completion, an expected duration of 18 months
Primary	Percent Change From Baseline Body Weight (Weight Loss)	Measurement of body weight pre to post intervention in each group	Baseline, 12 weeks, and 1 year
Secondary	Safety and Tolerability, Measured as Adverse Events	Number of participants with treatment-related adverse events in each group as evaluated by monthly phone questionnaire	1 year
Secondary	Quality of Life Scores at 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
Secondary	Quality of Life Scores at 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
Secondary	Quality of Life Scores at 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
Secondary	Mood at 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
Secondary	Mood at 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
Secondary	Mood at 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
Secondary	Change in Energy Intake	Self-reported energy intake	Baseline, 12 weeks and 1 year
Secondary	Change in Macronutrient Intake	Self-reported macronutrient intake	Baseline, 12 weeks and 1 year
Secondary	Serum Insulin-like Growth Factor-1 Levels at Baseline	Serum insulin-like growth factor-1 (IGF-1) levels will be evaluated in each group	Baseline
Secondary	Serum Insulin-like Growth Factor-1 Levels at 12 Weeks	Serum insulin-like growth factor-1 (IGF-1) levels will be evaluated in each group	12 Weeks
Secondary	Serum Insulin-like Growth Factor-1 Levels at 1 Year	Serum insulin-like growth factor-1 (IGF-1) levels will be evaluated in each group	1 Year
Secondary	Insulin-like Growth Factor Binding Protein-1 Levels at Baseline	Insulin-like growth factor binding protein-1 (IGFBP-1) levels will be evaluated in each group	Baseline
Secondary	Insulin-like Growth Factor Binding Protein-1 Levels at 12 Weeks	Insulin-like growth factor binding protein-1 (IGFBP-1) levels will be evaluated in each group	12 Weeks
Secondary	Insulin-like Growth Factor Binding Protein-1 Levels at 1 Year	Insulin-like growth factor binding protein-1 (IGFBP-1) levels will be evaluated in each group	1 Year
Secondary	Change in PBMC Ratio of pS6K/s6K	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
Secondary	Change in PBMC pAMPK/AMPK Expression	Ratio of peripheral blood mononuclear cell protein expression of phosphorylated AMP-activated kinase (AMPK) to AMPK in each group	Baseline and 1 year
Secondary	Percent Change in Total Kidney Volume by Magnetic Resonance Imaging (MRI)	Percent change from baseline in height adjusted total kidney volume by MRI in each group	Baseline and 1 year