Clinical trial NCT07022418: Formoterol in Diabetes
Official title: Prospective Randomized Placebo-controlled Pilot Trial of Formoterol in Patients With Diabetic Kidney Disease
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Diabetic Nephropathies
Diabetic Kidney Disease
Keywords: Diabetes
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
Collaborators: name: Dialysis Clinic, Inc.
First posted: 2025-06-15
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A double-blind randomized control feasibility trial of formoterol fumarate versus placebo in patients with type 2 diabetes and stage 2-3b chronic kidney disease (CKD) with albuminuria due to diabetic nephropathy (DN). Study participants will be randomized 1:1 to receive either formoterol fumarate or placebo, administered twice daily (morning and evening) by nebulization. The primary goal is to gather data on feasibility and effect sizes to properly power a future clinical trial.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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 the treating 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)
* Maintenance of all additional anti-HTN medications, insulin, oral and injectable non-insulin agents and cholesterol lowering medications prior to randomization
* Willing and able to comply with schedule of events and protocol requirements, including written informed consent.

Exclusion Criteria:

* on-diabetic kidney disease
* Type 1 diabetes
* 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 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

Primary outcomes:
measure: Feasibility: refusal rate and adherence during the 36-week treatment
timeFrame: 36 weeks
measure: To assess the safety, tolerability, and acceptability of the intervention with formoterol
timeFrame: 36 Weeks
measure: To perform preliminary efficacy testing and determine the variability of albuminuria
timeFrame: 36 Weeks
measure: To perform preliminary efficacy testing and determine the variability of eGFR.
timeFrame: 36 Weeks
Secondary outcomes:
measure: Safety Monitoring: Body Weight
timeFrame: 24 Weeks
measure: EKG Evaluations
timeFrame: 40 Weeks
measure: Adherence
timeFrame: 36 Weeks
measure: Adverse Events
timeFrame: 40 Weeks
measure: Tolerability and acceptability
timeFrame: 36 Weeks
measure: Liver Ultrasound Elastography
timeFrame: 36 Weeks
measure: Laboratory Evaluations: HbA1c
timeFrame: 40 Weeks
measure: Laboratory Evaluations: CMP
timeFrame: 40 Weeks
measure: Laboratory Evaluations: Urine Albumin
timeFrame: 40 Weeks
measure: Laboratory Evaluations: eGFR
timeFrame: 40 Weeks
measure: Safety Monitoring: Heart Rate
timeFrame: 40 Weeks
measure: Safety Monitoring: Blood Pressure
timeFrame: 40 Weeks
measure: Safety Monitoring: Respiratory Rate
timeFrame: 40 Weeks
measure: Safety Monitoring: Temperature
timeFrame: 40 Weeks
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Joshua Lipschutz, MD
role: PRINCIPAL_INVESTIGATOR
References: