Formoterol in Diabetes

Официальное название

Prospective Randomized Pilot Trial of Formoterol in Patients With Diabetic Kidney Disease

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Formoterol furmarate (20 μg)
  Investigators chose to use the long-acting β2-AR agonist, formoterol, because of its efficacy and safety profile in patients with COPD and because formoterol showed the most association with protection from progression of CKD in our retrospective study.

Первичные конечные точки

• Feasibility: refusal rate and adherence during the 36-week treatment [Срок оценки: 36 weeks]
• To assess the safety, tolerability, and acceptability of the intervention with formoterol [Срок оценки: 36 Weeks]
• To perform preliminary efficacy testing and determine the variability of albuminuria [Срок оценки: 36 Weeks]
• To perform preliminary efficacy testing and determine the variability of eGFR. [Срок оценки: 36 Weeks]

Вторичные конечные точки (12)

• Safety Monitoring: Body Weight [Срок оценки: 36 Weeks]
• EKG Evaluations [Срок оценки: 40 Weeks]
• Adherence [Срок оценки: 36 Weeks]
• Adverse Events [Срок оценки: 40 Weeks]
• Tolerability and acceptability [Срок оценки: 32 Weeks]
• Liver Ultrasound Elastography [Срок оценки: 36 Weeks]
• Laboratory Evaluations: HbA1c [Срок оценки: 40 Weeks]
• Laboratory Evaluations: CMP [Срок оценки: 40 Weeks]
• Laboratory Evaluations: Urine Albumin [Срок оценки: 40 Weeks]
• Laboratory Evaluations: eGFR [Срок оценки: 40 Weeks]
• Safety Monitoring: Heart Rate [Срок оценки: 40 Weeks]
• Safety Monitoring: Blood Pressure [Срок оценки: 40 Weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Medical University of South Carolina — Charleston

Идентификаторы

NCT: NCT07022418 · Pro00144030

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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