Glucose Metabolism in CFRD: Exploring the Role of CFTR Modulators in Metabolic Dysfunction
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Disposition Index in CFRD
研究概览
简要总结
The study aims to test whether use of CFTR modulators (ETI) improves fasting and post prandial glycemia by enhancing disposition index (DI) in individuals with CFRD with CFTR +ve mutation (at least one copy of F508del) on CFTR modulator (ETI) therapy (CFRDF508del+ETI). CFRD with a mutation that is not eligible for modulator therapy (CFRD-ETI) will be the control group.
详细描述
This is a mechanistic observational study. It is NOT a clinical trial. A physiological challenge of a single mixed meal tolerance test (MMTT) is administered, which will enable a comprehensive assessment of multiple parameters of glucose turnover, insulin secretion, insulin sensitivity and lipolysis in individuals with CFRD. The MMTT is the gold standard for measuring both insulin action and secretion simultaneously with glucose kinetics. The pilot study aims to test whether use of CFTR modulators (ETI) improves fasting and post prandial glycemia by enhancing disposition index (DI) in individuals with CFRD with CFTR +ve mutation (at least one copy of F508del) on CFTR modulator (ETI) therapy (CFRDF508del+ETI).
We plan to gather critical preliminary data on the following aspects of CFRD:
- Abnormalities in specific components (basal vs. static vs. dynamic) of beta-cell function in CFRDF508del+ETI and in CFRD-ETI individuals.
- Effects of ETI on components of beta cell function.
- Effects of CFTR mutation and of CFTR modulators (CFRDF508del+ETI) on insulin sensitivity and post prandial glucose turnover in CFRD.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 21 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Cystic Fibrosis Related Diabetes (CFRD)
- •Age 21-75 years at time of consent
- •BMI 19-50 kg/m2 (In Asians BMI is ~ 2 points lower for comparison so it is 17-48 kg/m2)
- •Creatinine ≤ 1.4 mg/dl in women and ≤ 1.5 mg/dl in men
- •HbA1c ≤ 11% lifestyle treatment or mono/combination therapy with oral hypoglycemic agents (e.g. metformin or sulphonylurea or SGLT2i) and preferably on insulin pump therapy (i.e., SAP, HCL) with or without CGM will be recruited. However, use of MDI (Multiple Daily Injections) of insulin, i.e., on basal-bolus insulin therapy will also be included. Most of our patients are on insulin therapy with very few on oral antidiabetes medications but we would like to offer them the choice of participation.
- •Subjects on FDA approved/recommended full doses of ETI will be offered participation. If dose adjustments of ETI are made after enrollment a discussion will be done with the primary care provider and HCSTOC as required.
- •Willing to be at a stable weight for duration of the study.
- •An understanding of and willingness to follow the protocol and sign the informed consent
- •Subjects meeting any of the
排除标准
- •at baseline will be excluded from study participation:
- •Exclusion Criteria:
- •Debilitating chronic disease
- •Anemia <10.0 gm/dL in females and <11.0 gm/dL in males
- •Symptoms of undiagnosed illness on history/exam
- •Abuse of alcohol or recreational drugs
- •Active hepatic disease (we will include only if less than 3X ULN for liver enzymes and no fibrosis on ultrasound). Transient elevations of liver enzymes will not exclude participation but will be discussed with the primary care provider and HCSTOC as required.
- •Current use of the following drugs and supplements:
- •i. Corticosteroids ii. Benzodiazepines iii. Opiates iv. Barbiturates v. Anticoagulant therapy vi. Any other medication that the investigator believes is a contraindication to the subject's participation
研究组 & 干预措施
CFRD F508del +ETI
CFRD with at least one copy of F508del currently on elexacaftor/tezacaftor/ivacaftor (CFRDF508del+ETI),
CFRD-ETI
CFRD with a mutation that is not eligible for modulator therapy (CFRD-ETI).
结局指标
主要结局
Disposition Index in CFRD
时间窗: Day 1 During the Mixed meal test
Disposition Index (DI - β-cell responsivity appropriate to the degree of insulin resistance) is higher in CFRDF508del+ETI when compared to CFRD with a mutation not eligible to be on ETI (CFRD-ETI).
次要结局
- Post prandial glucose turnover(Day 1 During the mixed meal test)
研究者
Rita Basu
Endowed Professor of Diabetes Science
University of Alabama at Birmingham