Daily Caloric Restriction and Intermittent Fasting in Overweight and Obese Adults With Autosomal Dominant Polycystic Kidney Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 2
- 主要终点
- Feasibility to Enroll and Retain Participants
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18-65 years
- •ADPKD diagnosis based on the modified Pei-Ravine criteria
- •BMI 25-45 kg/m^2
- •Normal to mildly declined renal function with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 by the CKD-EPI equation
- •Access to the internet with video chat capabilities
- •No plans for extended travel (>2 weeks) during the 3 month intesive period
- •Not currently participating in another interventional study or weight loss program
- •Ability to provide informed consent
排除标准
- •Diabetes mellitus (diagnosis or fasting glucose >126 mg/dL or Hemoglobin A1C >6.5%)
- •Current nicotine use or history of use in the past 12 months
- •Alcohol or substance abuse (self-report or undergoing treatment)
- •History of hospitalization or major surgery within the last 3 months
- •Untreated dyslipidemia (low density lipoprotein cholesterol > 190 mg/dL or triglycerides >400 mg/dL)
- •Uncontrolled hypertension (systolic blood pressure > 160 or diastolic blood pressure >100 mm Hg)
- •Pregnancy, lactation, or unwillingness to use adequate birth control
- •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)
- •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
- •Significant gastrointestinal disorders including: chronic malabsorptive conditions, peptic ulcer disease, Crohn's disease, ulcerative colitis, chronic diarrhea, or active gallbladder disease
- •Significant pulmonary disorders 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 (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
- •History of clinically diagnosed eating disorder including anorexia nervosa, bulimia, binge eating disorder
- •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.
- •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.
- •Current severe depression or history of severe depression within the previous year, based on DSM-IV-TR criteria for Major Depressive Episode.
- •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.
- •Inability to cooperate with/clinical contraindication for MRI including severe claustrophobia, implants, devices, or non-removable body piercings
结局指标
主要结局
Feasibility to Enroll and Retain Participants
时间窗: Through study completion, an expected duration of 18 months
Numbers of individuals pre-screened
Feasibility to Enroll Participants
时间窗: Through study completion, an expected duration of 18 months
Numbers of individuals screened
Percent Change From Baseline Body Weight (Weight Loss)
时间窗: Baseline, 12 weeks, and 1 year
Measurement of body weight pre to post intervention in each group
Feasibility to Retain Participants
时间窗: Through study completion, an expected duration of 18 months
Numbers of individuals enrolled
次要结局
- Quality of Life Scores at Baseline(Baseline)
- Change in PBMC Ratio of pS6K/s6K(Baseline and 1 year)
- Quality of Life Scores at 12 Weeks(12 Weeks)
- Quality of Life Scores at 1 Year(1 Year)
- Mood at 12 Weeks(12 Weeks)
- Mood at 1 Year(1 Year)
- Change in Energy Intake(Baseline, 12 weeks and 1 year)
- Serum Insulin-like Growth Factor-1 Levels at Baseline(Baseline)
- Insulin-like Growth Factor Binding Protein-1 Levels at Baseline(Baseline)
- Insulin-like Growth Factor Binding Protein-1 Levels at 1 Year(1 Year)
- Safety and Tolerability, Measured as Adverse Events(1 year)
- Mood at Baseline(Baseline)
- Serum Insulin-like Growth Factor-1 Levels at 12 Weeks(12 Weeks)
- Insulin-like Growth Factor Binding Protein-1 Levels at 12 Weeks(12 Weeks)
- Change in Macronutrient Intake(Baseline, 12 weeks and 1 year)
- Serum Insulin-like Growth Factor-1 Levels at 1 Year(1 Year)
- Change in PBMC pAMPK/AMPK Expression(Baseline and 1 year)
- Percent Change in Total Kidney Volume by Magnetic Resonance Imaging (MRI)(Baseline and 1 year)