Manipulating the Gut Microbiome Study

NCT03181828 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: #7230
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Urea Cycle Disorder

Keywords

CPSI deficiency; OTC Deficiency; AS Deficiency; AL Deficiency

Outcome Measures

Primary Outcomes (1)

• 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 +0 minutes, +30 minutes, +60 minutes, +90 minutes, +120 minutes, +180 minutes, and +240 minutes from time of infused [13C] Urea IV

Secondary Outcomes (1)

• Blood [13C]-Urea

  Time +O minutes, +30 minutes, +60 minutes, +90 minutes, +120 minutes, +180 minutes, and +240 minutes from time of [13C] Urea IV

Study Arms (2)

Acetohydroxamic Acid Oral Tablet then No Intervention

EXPERIMENTAL

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

No Intervention then Acetohydroxamic Acid Oral Tablet

EXPERIMENTAL

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

Interventions

Acetohydroxamic Acid Oral Tablet DRUG

A single oral dose of 60 mg/kg acetohydroxamic acid rounded to the nearest 250 mg tablet.

Also known as: Lithostat

Acetohydroxamic Acid Oral Tablet then No Intervention; No Intervention then Acetohydroxamic Acid Oral Tablet

No treatment OTHER

No treatment

Acetohydroxamic Acid Oral Tablet then No Intervention; No Intervention then Acetohydroxamic Acid Oral Tablet

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• For Group 1 (healthy adults):
• Ages 18-60 years
• Compliant with receiving medications orally and intravenously
• Compliant with providing blood and urine samples
• For Group 2 (adult UCD patients):
• Ages 18-60 years
• Compliant with receiving medications orally and intravenously
• Compliant with providing blood and urine samples
• Established diagnosis of CPSD, OTCD, ASSD or ASLD as follows:
• Diagnosis of CPS I deficiency, defined as decreased (less than 20 % of control) CPS I enzyme activity in liver or an identified pathogenic mutation
• Diagnosis of OTC deficiency, defined as the identification of a pathogenic mutation, linkage analysis in an affected family, less than 20% of control of OTC activity in the liver, or elevated urinary orotate (greater than 20 uM/mM) in a random sample or following allopurinol loading with absence of argininosuccinic acid
• Diagnosis of AS deficiency (Citrullinemia), defined as a greater than or equal to 10-fold elevation of citrulline in plasma, decreased AS enzyme activity in cultured skin fibroblasts or other appropriate tissue, or identification of a pathogenic mutation in the AS gene
• Diagnosis of AL deficiency (Argininosuccinic Aciduria, ASA), defined as the presence of argininosuccinic acid in the blood or urine, decreased AL enzyme activity in cultured skin fibroblasts or other appropriate tissue, or identification of a pathogenic mutation in the AL gene

You may not qualify if:

• For both Group 1 and Group 2:
• Current or prior Helicobacter pylori infection
• Chronic gastrointestinal illness (e.g., inflammatory bowel disease)
• Chronic renal failure
• Taking probiotic medications within a week of study start date
• Currently pregnant or lactating. Documentation of a negative pregnancy test within a week prior to testing is required, unless pre-menarchal or menopausal, experiencing menses that week, or other circumstances which preclude pregnancy (e.g. hysterectomy).
• Participation in any other clinical interventional trial or received experimental medication within the last 30 days
• Any clinical or laboratory abnormality or medical condition that, at the discretion of the investigator, may put the subject at an additional risk by participating in this study

Sponsors & Collaborators

• Nicholas Ah Mew: lead

Study Sites (1)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

MeSH Terms

Conditions

Urea Cycle Disorders, Inborn; Ornithine Carbamoyltransferase Deficiency Disease

Interventions

acetohydroxamic acid

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Genetic Diseases, X-Linked

Results Point of Contact

• Title: Dr. Nicholas Ah Mew
• Organization: Children's National

nahmew@childrensnational.org

2025452513

Study Officials

• Nicholas Ah Mew, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Model Details: This pilot randomized crossover study will first evaluate the impact of AHA versus non-AHA primarily on intestinal flora cleavage of an infused bolus of 13C-Urea and secondarily on other biomarkers in healthy adults before applying the same crossover design to UCD subjects.

Study Record Dates

• First Submitted: June 1, 2017
• First Posted: June 9, 2017
• Study Start: March 24, 2017
• Primary Completion: June 5, 2018
• Study Completion: June 5, 2018
• Last Updated: December 15, 2021
• Results First Posted: December 15, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)