A Phase 1 interventional study of Ammonium Chloride and Placebo in Heart Failure and Diuretic Resistance, sponsored by Yale University. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-22.
Sponsored by Yale University · Phase 1, Interventional, and Other
Randomized double-blind placebo-controlled crossover study design
Briefly, the protocol will begin with pre-study determination of diuretic response at the screening visit via administration of 10 mg IV bumetanide and measuring peak FENa. Participants may proceed to the subsequent study procedures. Participants will begin a study diet provided by the metabolic kitchen five days prior to Day 0. Beginning on day 0, participants will take either NH4Cl or placebo 75mmol twice daily. On day 1, the participant will return to study site and receives the first dose of their twice daily study medication as well as their regular loop diuretic dose given as IV bumetanide, followed by completion of the biospecimen collection protocol and a 24-hour urine collection. On day 2, participants will receive a full 150mmol dose at Hr-2 (75 mmol if pH\<7.3-7.25, no NH4Cl if pH\<7.25). 2 hours after the IV bumetanide is given, 100mmol of sodium bicarbonate in 750ml of 5% dextrose will be administered to participants that received NH4Cl or 750 ml of lactated Ringer's solution to participants that received placebo (provided blinded by the investigational pharmacy).
After this visit, a washout period will be conducted before the above procedures are repeated with the alternate study medication. The washout period will be a minimum of 10 days and a maximum of 28 days. Five days prior to the end of the washout period, the participant will resume the study diet until the end of the study on day 18. On day 16, the participant will be crossed over to the alternate therapy (NH4Cl or placebo). On day 17, the participant will complete the same procedures as day 1 of the first arm. On day 18, the participant will complete the same procedures as day 2 of the first arm.
The administration of Bendroflumethiazide will occur under a separate ancillary protocol
5,697 studies on the registry are indexed under Heart Failure; 1,219 are open to participants now.
This study's planned enrollment of 50 is below the median of 72 across 3,733 interventional studies indexed under Heart Failure.
Browse Heart Failure studies →Yale University is the lead sponsor of 1,724 studies on the registry; 298 are open to participants now.
Of its 210 completed or terminated interventional studies of FDA-regulated products, 126 (60%) have results posted.
Counted across the registry records on this site, refreshed daily.
Objective evidence of diuretic resistance to a 10mg bumetanide challenge (screening visit may occur under this protocol or HIC2000032328 or HIC2000034315) defined as:
And at least one of the following criteria:
Exclusion Criteria:
Participants will be randomized to ammonium chloride vs placebo. On Day 0 and 1, the participant will take ammonium chloride or placebo 75 mmol twice daily. On Day 2, the participant will take ammonium chloride 150 mmol or placebo once
Drug: Ammonium Chloride
Participants will be randomized to ammonium chloride vs placebo. On Day 0 and 1, the participant will take ammonium chloride or placebo 75 mmol twice daily. On Day 2, the participant will take ammonium chloride 150 mmol or placebo once
Drug: Placebo
Participants will be randomized to receive either ammonium chloride or placebo. Participants will receive randomized drug in combination with IV bumetanide, bendroflumethiazide, and amiloride. Following a washout period, participants will be crossed over to the alternate drug.
Participants will be randomized to receive either ammonium chloride or placebo. Participants will receive randomized drug in combination with IV bumetanide, bendroflumethiazide, and amiloride. Following a washout period, participants will be crossed over to the alternate drug.
Change of distal sodium reabsorption(ADRNa) between NH4Cl vs. placebo study visits
Comparison of ADRNa between NH4Cl vs. placebo during study visits using fractional excretion of lithium and fractional excretion of sodium to calculate the ADRNa.
Time frame: Day 0 vs Day 1
Change of distal sodium reabsorption(ADRNa) between NH4Cl vs. placebo study visits
Comparison of ADRNa between NH4Cl vs. placebo during study visits using fractional excretion of lithium and fractional excretion of sodium to calculate the ADRNa.
Time frame: Day 2 vs Day 18
Plan to share: No
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