A Pilot and Feasibility Study to Evaluate High vs Low Glycemic Index Mixed Meal Tolerance Test in Adolescents and Young Adults With Cystic Fibrosis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Investigator Fidelity
研究概览
简要总结
The goal of this study is to determine the extent to which excess dietary simple sugars serve as a secondary mediating factor in Cystic fibrosis-related diabetes (CFRD) development. The main questions it aims to answer are:
- Whether conducting a randomized 2x2 factorial design that evaluates acute postprandial changes in glucose over 2 hours following ingestion of a mixed meal challenge that varies by glycemic index and consumption of a sugar-sweetened beverage is acceptable and feasible.
- What are the preliminary changes in postprandial hyperglycemia, islet cell function, and incretin response to a high or low Glycemic Index mixed meal tolerance test (MMTT) with and without Sugar-Sweetened Beverages (SSB) in adolescents and young adults with CF
Participants will be randomized to a mixed diet and blood will be drawn before and after the mixed meal challenge.
详细描述
Cystic fibrosis-related diabetes (CFRD) is one of the most common co-morbidities seen in CF and significantly increases morbidity and mortality. The prevalence of CFRD increases with age with approximately 20% of adolescents and 50% of adults in the 3rd and 4th decade of life carrying the diagnosis. Although a diagnosis of CFRD is uncommon in children less than 10 years of age, research studies show that abnormal glucose tolerance is found in about 40% of CF toddlers and school-age children. Mechanisms leading to the development of CFRD are incompletely understood. For several years, the predominant theory of pancreatic endocrine dysfunction was based on the theory of "collateral damage" which results in impairment of β-cell function due to loss of islet cells. In addition to experiencing reduced beta cell mass, individuals with CF have a diminished incretin effect that contributes to impaired insulin secretion. Postprandial hyperglycemia is not uncommon for individuals with CF irrespective of their glucose tolerance and during an OGTT failure to suppress glucagon results in hyperglycemia. Unfortunately, mechanisms involved in dysregulated glucagon release and its contribution to hyperglycemia in CF are poorly understood.
The CF diet is typically high in energy-dense, nutrient-poor foods. Individuals with CF require high-energy, high-fat diets to maintain their hypermetabolic state and offset malabsorption, with current CF dietary guidelines recommending an energy intake of 1.2 to 1.5 times that of the general population. To date, there is a paucity of studies that rigorously investigate the metabolic sequelae that high GI foods and SSB have on the metabolic profile of individuals with CF. The study team proposes that a diet high is SSBs and high GI foods induces more oxidative stress due to postprandial hyperglycemia, impairs insulin secretion, and exacerbates glucose abnormalities in CF.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •English speaking
- •Diagnosis of CF based on the presence of two known CF causing mutations and/or positive sweat test
- •Pancreatic insufficiency
- •Baseline dietary consumption of >10% total kcal from added sugars and self-reported consumption of >/= sugar-sweetened beverages per week
排除标准
- •Current use or anticipated use of medication that is known to raise or lower blood glucose in the past 4 weeks.
- •Oral or IV glucocorticoid current or previous use in the past 4 weeks will prohibit enrollment in the study.
- •Recent pulmonary exacerbation within 3 weeks of enrollment and/or an acute illness requiring a change in antibiotics will also exclude participants.
- •BMI below the 5th percentile or greater than the 95th percentile for age and sex
- •FEV1 <40% or awaiting a lung transplant;
- •Prior lung or liver transplant or kidney or liver dysfunction.
- •Use of CFTR modulators is not an exclusion criterion. Rather, for patients recently started on CFTR modulators, we will wait to enroll in the study until on CFTR modulator for at least 2 months.
- •Diagnosis of CF liver disease.
- •Uncontrolled exocrine pancreatic insufficiency/malabsorption
- •Diagnosis of CFRD
- •G-tube feeds (bolus and/or continuous)
- •Current enrollment in another intervention study
- •Changes in diet to lose or gain weight
- •Gluten allergy or intolerance
- •Current pregnancy or lactation or plans to become pregnant during study period
- •History of drug or alcohol abuse
- •Restrictive dietary patterns (e.g, vegan, ketogenic, intermittent fasting) for more than one month within the last two months prior to screening.
- •More than 5% body weight change within 2 months of screening visit or Day 1 of mixed meal tolerance test
结局指标
主要结局
Investigator Fidelity
时间窗: 2 years
Capacity of the research team to manage the intervention. Goal is \>85%.
Retention Rates
时间窗: 2 years
Retention rates as the participants complete the intervention. Goal is \>80%
Recruitment
时间窗: 2 years
Length of time it takes to recruit enough participants into the study. Goal is to recruit all patients by the end of second quater of the second year.
Recruitment Rate
时间窗: 2 years
Recruitment rate of participants. Goal is to recruit 3 participants per month.
Participant Fidelity
时间窗: 2 years
Feasibility of data collection, including primary and secondary outcome measures. Goal is \>85%
Refusal Rate
时间窗: 2 years
Refusal rates for participation. 20%of screened participants will refuse to participate
Acceptability
时间窗: 2 years
Acceptability and burden of intervention on participants. Likert scale response of \>3(out of 5) on post study evaluation that study is not burdensome and acceptable
次要结局
- Change in plasma Cystine (CySS)(Baseline, 2 hours)
- Insulinogenic index(Baseline, 30 mins)
- Change in plasma Eh Cys/CySS(Baseline, 2 hours)
- Changes in Plasma Incretins: glucagon-like peptide-1 (GLP-1)(Baseline, 2 hours)
- Whole body insulin sensitivity index (WBISI-Matsuda)(2 hours)
- Changes in Plasma insulin(Baseline, 2 hours)
- Changes in Plasma Glucagon(Baseline, 2 hours)
- Change in plasma Cysteine (Cys)(Baseline, 2 hours)
- Change in plasma Glutathione (GSH)(Baseline, 2 hours)
- Change in plasma Glutathione Disulfide (GSSG)(Baseline, 2 hours)
- Change in redox potentials (EhCys/ CySS and EhGSH/GSSG)(Baseline, 2 hours)
- Changes in Plasma C-peptide(Baseline, 2 hours)
- Disposition Index(2 hours)
- Change in incremental glucose AUC(Baseline, 120 minutes)
- Changes in Plasma Incretins: total glucose-dependent insulinotropic polypeptide (GIP)(Baseline, 2 hours)