Prospective Randomized Pilot Trial of Formoterol in Patients With Diabetic Kidney Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Feasibility: refusal rate and adherence during the 36-week treatment
研究概览
简要总结
The purpose of the study is to evaluate if formoterol fumarate is effective in treating patients with diabetic kidney disease. Study participants will be randomly assigned to either receive formoterol fumarate (in addition to their current standard of care treatment) or standard of care treatment only. Study participants will have a 50% chance of receiving formoterol fumarate and a 50% chance of not receiving formoterol fumarate. Both groups will continue their standard of care treatment during the study. The primary goal is to gather data on feasibility and effect sizes to properly power a future clinical trial.
详细描述
Glomerular function is highly dependent on specialized cells known as podocytes, which are critical components of glomeruli. Diseases affecting podocytes and the glomerulus, such as diabetes, are the leading causes of ESKD, and there are no specific therapies that restore injury-induced loss of podocyte structure and function. It was previously shown using mouse models of podocyte injury that formoterol fumarate, a long-acting β2-AR agonist given four hours following injury, when glomerular dysfunction is already established, restored glomerular structure, significantly reduced proteinuria, and accelerated recovery of glomerular function. To determine if a similar effect occurred in CKD, specifically DN, investigators used streptozotocin, a murine model of type 1 diabetes, and a high fat diet (HFD), a murine model of type 2 diabetes, to examine the role of formoterol fumarate in DN. Following formoterol fumarate treatment, there was a marked recovery from and reversal of DN in the streptozotocin and HFD mice treated with formoterol fumarate compared to those treated with vehicle alone at the ultrastructural, histological, and functional levels. Investigators also performed a competing risk regression in Veterans aged 65 or over with incident CKD stage 4 to compare the rate of ESKD progression in Veterans without and with COPD, who use β2-AR agonists. Investigators found a 25.6% reduction in the rate of ESKD in Veterans with COPD compared to those without4. In a second cohort of Veterans, Investigators demonstrated significantly slower progression from CKD stage 3 to CKD stage 5 in patients with COPD compared to those without COPD. Together these data indicate that β2-AR agonists, especially formoterol fumarate, may be a novel treatment for DN.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 18-75
- •Diagnosis of type 2 diabetes according to American Diabetes Association (ADA) criteria
- •On stable medical therapy for at least 3 months
- •Stage CKD G2 to G3b; A2-A3 as defined by eGFR with no requirement for renal biopsy for diagnosis
- •Diabetic kidney disease as per Nephrologist
- •Urinary albumin to creatinine excretion rate (UACR) 200-5000 mg/g/24hrs on at least two occasions (one of these can be a spot UACR)
- •HbA1c <8%
- •Receiving stable doses of ACE inhibitor or ARB therapy prior to screening (at least 3 months, unless contraindicated) and/or a stable dose of an SGLT inhibitor (at least 3 months preceding enrollment)
- •Receiving stable doses of all additional anti-HTN medications, insulin, oral and injectable non-insulin agents and cholesterol lowering medications at least 3 months prior (unless contraindicated) to randomization and agree to maintain until the study's conclusion.
- •Willing and able to comply with schedule of events and protocol requirements, including written informed consent.
排除标准
- •Female subjects who are pregnant or breast feeding or who plan on becoming pregnant
- •Currently take beta-agonists
- •Organ transplant recipients
- •Any history of New York Heart Association (NYHA) class III/IV heart failure or recent history of serious heart problem (CABG, stroke, MI) in the past 12 months
- •Any history of asthma
- •Patients with serum potassium levels <3.5 mEQ/L
- •Patients with uncontrolled HTN SBP >150mmHg, DBP >95mmHg
- •EKG showing QTc elongation or tachyarrhythmia; including sinus tachycardia >100bpm
- •Contraindications to formoterol fumarate (hypersensitivity, including patients with known hypersensitivity to ACE inhibitors or ARBs)
- •Advanced organ failure
- •Untreated/uncontrolled cardiovascular, pulmonary, or gastrointestinal disease
- •Patients with BMI >50
- •Active untreated cancer
- •Alcohol or drug abuse in the past 6 months
- •Being involuntarily incarcerated
- •Participating in another interventional study
- •Unable or unwilling to do the 36-week intervention
研究组 & 干预措施
Formoterol Fumarate + Standard of Care Treatment
Formoterol Fumarate Inhalation Solution as one 20 mcg unit-dose vial administered twice daily (morning and evening) by nebulization (in addition to standard of care treatment)
干预措施: Formoterol furmarate (20 μg) (Drug)
Standard of Care Only
Standard of Care Treatment Only
结局指标
主要结局
Feasibility: refusal rate and adherence during the 36-week treatment
时间窗: 36 weeks
The primary measures of feasibility will be study refusal rate and adherence during the 36-week treatment. Refusal rate will be the percentage of individuals who are offered the opportunity to enroll but choose not to accept it. Adherence will be defined as the proportion of doses taken during the 36-week treatment period. For patients who fail to complete the study, adherence will be estimated as the number of doses they report taking for visits at which they are present over the total number of doses they should have received.
To assess the safety, tolerability, and acceptability of the intervention with formoterol
时间窗: 36 Weeks
Rates of adverse events and safety measures will be compared between groups. The investigators will assess adherence with the intervention and study medication.
To perform preliminary efficacy testing and determine the variability of albuminuria
时间窗: 36 Weeks
Changes in albuminuria will be compared between groups to provide preliminary efficacy testing.
To perform preliminary efficacy testing and determine the variability of eGFR.
时间窗: 36 Weeks
Changes in eGFR will be compared between groups to provide preliminary efficacy testing. eGFR will be assessed using the CKD-Epi Formula.
次要结局
- Safety Monitoring: Body Weight(36 Weeks)
- EKG Evaluations(40 Weeks)
- Adherence(36 Weeks)
- Adverse Events(40 Weeks)
- Tolerability and acceptability(32 Weeks)
- Liver Ultrasound Elastography(36 Weeks)
- Laboratory Evaluations: HbA1c(40 Weeks)
- Laboratory Evaluations: CMP(40 Weeks)
- Laboratory Evaluations: Urine Albumin(40 Weeks)
- Laboratory Evaluations: eGFR(40 Weeks)
- Safety Monitoring: Heart Rate(40 Weeks)
- Safety Monitoring: Blood Pressure(40 Weeks)
- Safety Monitoring: Respiratory Rate(40 Weeks)
- Safety Monitoring: Temperature(40 Weeks)
研究者
Joshua Lipschutz
Professor-Faculty
Medical University of South Carolina