A Phase 1/2 interventional study of Acetohydroxamic Acid Oral Tablet and No treatment in Urea Cycle Disorder, sponsored by Nicholas Ah Mew. Terminated at 1 site in United States. Open to participants aged 18 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-12-15.
Sponsored by Nicholas Ah Mew · Phase 1/2, Interventional, and Treatment
Among 40 studies in Urea Cycle Disorders, Inborn with a site in United States — 9 open to participants now, 12 under way, 1 of them phase 3. Urea Cycle Disorders, Inborn · United States.
Among the 40 studies in Urea Cycle Disorders, Inborn with a site in United States, this one is the 23rd largest by enrollment of the 24 interventional ones that give a count, is one of 5 that started in 2017, is one of 3 in phase 1/2, and was the 26th registered.
66 studies on the registry are indexed under Urea Cycle Disorders, Inborn; 14 are open to participants now.
Browse Urea Cycle Disorders, Inborn studies →9 of the 40 studies in Urea Cycle Disorders, Inborn with a site in United States are open now. Recruiting first, the newest first:
Rebecca Ahrens-Nicklas · Sites in United States
Ages 24 hrs–5 yrs
St. Jude Children's Research Hospital · Sites in United States
Ages 16–40 · Healthy volunteers
Sequitur Health Corp. · Sites in United States
Ages 12+
iECURE, Inc. · Sites in United States, France, United Kingdom
Ages 7 mo–15 mo
Baylor College of Medicine · Sites in United States
A study can be open while its sites in United States have not opened yet or have stopped. Only those recruiting at a site in United States →
Of the 12 Urea Cycle Disorders, Inborn studies recruiting now, 5 (42%) set no upper age limit and 7 (58%) stop at 75 or younger; 11 take children under 18; 4 take healthy volunteers.
This study: 18 Years to 60 Years · all sexes · healthy volunteers too.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
40 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 6 · Phase 2 9 · Phase 3 4 · Phase 4 3
First in 1999; this study’s year is marked. 5 started in 2017.
This study's enrollment of 4 is below the median of 17 across 39 interventional studies indexed under Urea Cycle Disorders, Inborn.
Median enrollment 16 across the 24 interventional studies, 51 across the 16 observational. Of the 27 that completed or were terminated, 16 (59%) have results posted.
This tab as a report to print or save as PDF → With an account.
18 of 40 have an industry lead sponsor. The 10 most frequent:
Nicholas Ah Mew is the lead sponsor of 2 studies on the registry; 1 is open to participants now.
Nicholas Ah Mew has 2 studies filed under Urea Cycle Disorders, Inborn — fewer than ten, so there is no comparison to draw.
2 of the studies in Urea Cycle Disorders, Inborn with a site in United States that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT04612764Baylor College of MedicineLiver Disease in Urea Cycle Disorders | 2026-12-31 |
| NCT06953505Sequitur Health Corp.At Home Ammonia Monitoring of Inborn Errors of Ammonia Metabolism | 2027-07 |
Add all 2 to your calendar (.ics) → With an account.
Among the 40 studies in Urea Cycle Disorders, Inborn with a site in United States, from their registry updates:
Nothing recorded among them since 2026-09-25.
This tab as a report to print or save as PDF → With an account.
The objective is to determine if acetohydroxamic acid (AHA) can prevent hydrolysis of urea by inhibiting the bacterial urease of gut flora of both healthy control adults as well as adults with urea cycle disorders
This project will study the efficacy and safety of the pharmacologic blockade of urease in the nitrogen salvage pathway of intestinal microbes in subjects with partial urea cycle disorders. Additional trapping of ammonia as excretable urea may result in improved nitrogen excretion and reduced ammonia levels.
Urea cycle disorders (UCDs) are a group of disorders resulting from a complete or partial deficiency of one of the 6 enzymes or 2 transporters that comprise the urea cycle, the essential biochemical pathway which converts toxic ammonia into urea. These disorders have as a common feature, a reduced or complete inability to convert ammonia into urea, thereby resulting in high ammonia levels, or hyperammonemia. If untreated, hyperammonemia may result acutely in lethargy and coma, and chronically in intellectual disability. Current treatment for hyperammonemia is suboptimal, thus the search for new treatments is critical.
The urease inhibitor, acetohydroxamic acid (AHA, Lithostat®, Mission Pharmacal), is an FDA-approved product for another indication- the treatment of struvite nephrolithiasis in chronic urinary tract infections in both adults and children.
It is known that many urea-splitting bacteria also exist in the gut, and that in healthy individuals, approximately 15-30% of blood urea is degraded via gut bacteria into ammonia3, which returns to the liver via the portal vein, only to be recycled into urea. This percentage of degraded urea may even be greater in patients with urea cycle disorders, who are on a low protein-diet4 and whose gastrointestinal contents thus likely have lower nitrogen content, promoting bacterial recycling of nitrogen from available urea. Additionally, urea hydrolysis has been shown to be greatest in infants5, precisely the age at which hyperammonemic episodes are the most frequent in UCD patients.
We intend to study if AHA can inhibit gut bacteria degradation of urea, thereby reducing the quantity of ammonia returning to the liver. We intend to investigate this by studying subjects on two occasions at least 3 days apart:
On the first occasion, subjects will receive an intravenous dose of 13C-urea. Following the intravenous bolus of 13C-urea, over the subsequent 4 hours, we will collect several sequential measurements of blood and urine biomarkers from an IV catheter placed in the other arm. The intent is to obtain baseline 13CO2 kinetics in the subject.
On the second occasion, subjects will first receive an oral dose of AHA approximately 1 hour prior to the intravenous 13C-urea dose. Similar sequential measurements of blood and urine biomarkers will be performed. The intent is to observe a reduction in 13CO2 when AHA is administered.
We intend to initially study a cohort of unaffected adult subjects. If successful, we will study adults with partial urea cycle disorders.
This study will be conducted in the Clinical Research Center (CRC) of the Clinical and Translational Research Institute (CTSI) of Children's National Medical Center (CNMC).
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
For Group 2 (adult UCD patients):
Established diagnosis of CPSD, OTCD, ASSD or ASLD as follows:
Exclusion Criteria:
Participants receive a single oral dose of 60 mg/kg acetohydroxamic acid (rounded to the nearest 250 mg) in the fasted state on the morning of the study. After completion of the 4-h study, participants then enter a wash-out period of 3 days. Participants then completed an identical 4-h study in the fasted state without acetohydroxamic acid.
Drug: Acetohydroxamic Acid Oral Tablet · Other: No treatment
Participants completed a 4-h study in the fasted state without acetohydroxamic acid. 3 days later, participants then completed an identical 4-h study in the fasted state, after having received a single oral dose of 60 mg/kg acetohydroxamic acid (rounded to the nearest 250 mg).
Drug: Acetohydroxamic Acid Oral Tablet · Other: No treatment
A single oral dose of 60 mg/kg acetohydroxamic acid rounded to the nearest 250 mg tablet.
Also known as: Lithostat
No treatment
Atom Percent Excess of 13CO2
Difference in the % enrichment of Carbon-13 in blood CO2 as compared to baseline measurement, at sequential time points, after a single bolus of intravenous \[13C\]-Urea,
Time frame: Time +0 minutes, +30 minutes, +60 minutes, +90 minutes, +120 minutes, +180 minutes, and +240 minutes from time of infused [13C] Urea IV
Blood [13C]-Urea
Concentration of urea labeled with Carbon-13
Time frame: Time +O minutes, +30 minutes, +60 minutes, +90 minutes, +120 minutes, +180 minutes, and +240 minutes from time of [13C] Urea IV
| Milestone | No Intervention, Then Acetohydroxamic Acid Oral Tablet [Lithostat] | Acetohydroxamic Acid Oral Tablet [Lithostat], Then No Intervention |
|---|---|---|
| Started | 2 | 2 |
| Completed | 2 | 2 |
| Not completed | 0 | 0 |
Difference in the % enrichment of Carbon-13 in blood CO2 as compared to baseline measurement, at sequential time points, after a single bolus of intravenous \[13C\]-Urea,
| Atom % Excess | Acetohydroxamic Acid Oral Tablet | No Intervention |
|---|---|---|
| 0 min | 0 ± 0 | 0 ± 0 |
| 30 min | -0.00216 ± 0.00376 | 0.00268 ± 0.00531 |
| 60 min | 0.000959 ± 0.00130 | 0.000318 ± 0.0105 |
| 90 min | 0.00129 ± 0.00101 | 0.00336 ± 0.00583 |
| 120 min | 0.00152 ± 0.00117 | 0.00277 ± 0.00528 |
| 180 | -0.00392 ± 0.00561 | -0.000982 ± 0.00122 |
| 240 | -0.000537 ± 0.00386 | 0.00203 ± 0.00617 |
Concentration of urea labeled with Carbon-13
| micromol/L | Acetohydroxamic Acid Oral Tablet | No Intervention |
|---|---|---|
| 0 Min | 0 ± 0 | 0 ± 0 |
| 30 Min | 174.9 ± 43.57 | 199.5 ± 9.12 |
| 60 Min | 151.9 ± 30.05 | 165.2 ± 6.07 |
| 90 Min | 140.9 ± 12.48 | 152.4 ± 6.14 |
| 120 Min | 137.3 ± 9.58 | 136.8 ± 6.65 |
| 180 Min | 127.8 ± 9.87 | 126.5 ± 7.78 |
| 240 | 119.9 ± 11.93 | 117.2 ± 9.95 |
Collected over 1 week. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Acetohydroxamic Acid Oral Tablet | 0/4 (0%) | 0/4 (0%) | 4/4 (100%) |
| No Intervention | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) |
| Event | Acetohydroxamic Acid Oral Tablet | No Intervention |
|---|---|---|
| HeadacheNervous system disorders | 4/4 | 0/4 |
| NauseaNervous system disorders | 2/4 | 0/4 |
All the enrolled participants have been healthy adults.
| Age, Categorical(Participants) | No Intervention Then Acetohydroxamic Acid Oral Tablet | Acetohydroxamic Acid Oral Tablet Then No Intervention | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 2 | 2 | 4 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(years) | No Intervention Then Acetohydroxamic Acid Oral Tablet | Acetohydroxamic Acid Oral Tablet Then No Intervention | Total |
|---|---|---|---|
| Mean | 47 (36 to 58) | 40 (38 to 42) | 43.5 (36 to 58) |
| Sex: Female, Male(Participants) | No Intervention Then Acetohydroxamic Acid Oral Tablet | Acetohydroxamic Acid Oral Tablet Then No Intervention | Total |
|---|---|---|---|
| Female | 1 | 1 | 2 |
| Male | 1 | 1 | 2 |
| Race (NIH/OMB)(Participants) | No Intervention Then Acetohydroxamic Acid Oral Tablet | Acetohydroxamic Acid Oral Tablet Then No Intervention | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 1 | 0 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 2 | 3 |
| White | 0 | 0 | 0 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | No Intervention Then Acetohydroxamic Acid Oral Tablet | Acetohydroxamic Acid Oral Tablet Then No Intervention | Total |
|---|---|---|---|
| United States | 2 | 2 | 4 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Mar 2017 to primary completion in Jun 2018, 14 months.
Results were first posted in Dec 2021, 3 years 6 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is terminated, as verified in Nov 2021. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Urea Cycle Disorders, Inborn →
Nicholas Ah Mew