Clostridium Difficile InfectionPhase 2NCT02053350
Alanyl-glutamine Supplementation of Standard Treatment for C. Difficile Infection
A Phase 2 study testing Alanyl-glutamine in people with Clostridium Difficile Infection, run by University of Virginia at 1 site in United States.
Trial summary
The aim of this study is to test the efficacy of alanyl-glutamine supplementation in the treatment of C. difficile infection. We hypothesize that alanyl-glutamine when given with standard antibiotic treatment for C. difficile infection will decrease diarrhea, mortality and recurrent disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clostridium Difficile Infection
- What is being tested?
- Alanyl-glutamine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2015to 5 Apr 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult of either gender, 18 years or older, with C. difficile infection (CDI)
- Diarrhea associated with C. difficile positive stool assay
- Within 48 hours of receiving either metronidazole for mild-moderate disease or vancomycin for severe uncomplicated disease
- Admitted in the hospital at the time of enrollment
- Ability to provide informed consent
- Have an understanding of study procedures
- Ability to comply with study procedures for the entire length of the study
Who cannot join
- Hypotension or shock
- Megacolon or moderate to severe ileus
- Acute abdomen
- Severe leukocytosis (WBC > 20,000 cells /µL)
- Admission to intensive care unit on enrollment
- Inability to tolerate oral medication
Show all 15Show fewer
- Other known etiology of diarrhea (e.g. other enteric pathogen, other intestinal disease)
- Inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis)
- Enrollment in another investigational drug trial
- Currently receiving other alternative treatment for CDI (e.g. antibiotics other than metronidazole or vancomycin; probiotics; immunoglobulin therapy; fecal transplant)
- Pregnancy
- Unavailable for follow-up visits
- Life expectancy of < 6 months
- Chronic liver disease or in subjects without known liver disease, ALT > 3x normal
- Chronic kidney disease or in subjects without known kidney disease, estimated Creatinine clearance of < 30 ml/min, even after rehydration
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia Health System
Charlottesville, Virginia, 22908
About this study
Official title: Alanyl-glutamine Supplementation of Standard Treatment for C. Difficile Infection: A Randomized, Double-blind, Placebo-controlled Trial
The aim of this study is to test the efficacy of alanyl-glutamine supplementation in the treatment of C. difficile infection. We hypothesize that alanyl-glutamine when given with standard antibiotic treatment for C. difficile infection will decrease diarrhea, mortality and recurrent disease.
Read the detailed description
This is a Phase II randomized, placebo-controlled, double-blinded, dose-ranging study to determine optimal effective dose and safety of AQ between 0, 4, 24, and 44 g doses administered orally for ten days concurrent with standard treatment (oral vancomycin at UVa) among first time incident cases of uncomplicated CDI in hospitalized persons age 50 and older. Our hypothesis is that AQ will reduce recurrence (primary outcome) and mortality (secondary outcome) at 60 days post-treatment. Furthermore, we hypothesize that alanyl-glutamine supplementation will be associated with decreased intestinal and systemic inflammation and improvement of intestinal microbial and metabolic profiles. We plan to enroll 260 patients, equally divided into 4 arms. Upon enrollment, participants will be randomized to either receive AQ at 4, 24, or 44 g or placebo (water). Study agent is administered once a day, orally or enterally, if feeding tube is present. Because we are enrolling subjects over a longer period of time, we will utilize block randomization to ensure that relative temporal balance is maintained throughout the trial. Participants will be followed up daily during treatment for adverse event monitoring and weekly for 60 days post-treatment for recurrences and survival. Blood, urine and stool specimens will be collected at days 0, 10 and 70 to assay for markers of inflammation and microbial and metabolic profiling.
The data set utilized for all initial baseline feature and demographic reporting will be the Intention to Treat Analysis Dataset, which will be comprised of all randomized participants. The primary dataset will be a Modified Intention to Treat Analysis Dataset for all endpoints, comprised of all participants who took at least one dose of study intervention (placebo or treatment), regardless of completeness of follow-up outcome data. The Safety Analysis Dataset will be all participants who took at least one dose of study intervention. The Per Protocol Analysis Dataset will be those patients who took at least 9 doses of study intervention for 9 days of the treatment period (10 days). Analysis will utilize ANOVA unless statistically significant differences in the distribution of baseline characteristics or features of non-normality are detected and relevant, at which point contingency utilization of ANCOVA, logistic regression, or other approaches as appropriate will be implemented. Treatment group level rates will be presented as incidence risk ratios relative to the control (placebo) group with 95% confidence intervals.
Safety endpoints will be evaluated on an individual AE by AE event via the DSMB and utilizing summary statistics during treatment and through duration of follow up. Adverse events will be presented by System Organ Class and will include information on start and stop date, severity, projected relationship, expectedness, and outcome and duration (the latter two after the event is considered to have concluded).
- Conditions
- Clostridium Difficile Infection
- Being tested
- Alanyl-glutamine
- Keywords
- Clostridium difficile, glutamine, diarrhea, alanyl-glutamine
- Medical subject headings
- Clostridium Infections, Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alanyl-glutamineDrug
Also called alagln
Alanyl-glutamine, 44g, taken by mouth daily for 10 days
| Study group | Role | What they receive |
|---|---|---|
| Alanyl-glutamine | Experimental | Alanyl-glutamine, 44g, taken by mouth daily for 10 days. Receives: Drug: Alanyl-glutamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Recurrent C. Difficile Infection
Day 40 clinical failure - clinical failure includes death or CDI recurrence assessed 40 days post randomization or lack of clinical cure
Measured: At day forty
Mortality
Death from any cause at days 40, 70 and 190
Measured: Up to 6 months after end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2014 (estimated)
- Study startApr 2015
- Primary completion5 Apr 2017
- Study completion5 Apr 2017
Why it stopped: Funding ended
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Clostridium Difficile InfectionStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Cirle Warren, MD, University of Virginia
- Investigators
- Cirle A. Warren, M.D., Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02053350
- Sponsor's protocol ID
- 17576
- Other IDs
- 17576 Protocol_Alanyl_Glutami
- Status last verified
- May 2022
- First submitted
- 29 Jan 2014
- Last updated
- 7 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Alanyl-glutamine Supplementation of Standard Treatment for C. Difficile Infection: A Randomized, Double-blind, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT02053350
- Acronym / sponsor ID
- 17576
- Conditions
- Clostridium Difficile Infection
- Keywords
- Clostridium difficile, glutamine, diarrhea, alanyl-glutamine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding ended
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- Apr 2015
- Primary completion
- 5 Apr 2017 (actual)
- Study completion
- 5 Apr 2017 (actual)
- First posted
- 3 Feb 2014 (estimated)
- Results
- Posted 7 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to test the efficacy of alanyl-glutamine supplementation in the treatment of C. difficile infection. We hypothesize that alanyl-glutamine when given with standard antibiotic treatment for C. difficile infection will decrease diarrhea, mortality and recurrent disease.
Detailed description
This is a Phase II randomized, placebo-controlled, double-blinded, dose-ranging study to determine optimal effective dose and safety of AQ between 0, 4, 24, and 44 g doses administered orally for ten days concurrent with standard treatment (oral vancomycin at UVa) among first time incident cases of uncomplicated CDI in hospitalized persons age 50 and older. Our hypothesis is that AQ will reduce recurrence (primary outcome) and mortality (secondary outcome) at 60 days post-treatment. Furthermore, we hypothesize that alanyl-glutamine supplementation will be associated with decreased intestinal and systemic inflammation and improvement of intestinal microbial and metabolic profiles. We plan to enroll 260 patients, equally divided into 4 arms. Upon enrollment, participants will be randomized to either receive AQ at 4, 24, or 44 g or placebo (water). Study agent is administered once a day, orally or enterally, if feeding tube is present. Because we are enrolling subjects over a longer period of time, we will utilize block randomization to ensure that relative temporal balance is maintained throughout the trial. Participants will be followed up daily during treatment for adverse event monitoring and weekly for 60 days post-treatment for recurrences and survival. Blood, urine and stool specimens will be collected at days 0, 10 and 70 to assay for markers of inflammation and microbial and metabolic profiling.
The data set utilized for all initial baseline feature and demographic reporting will be the Intention to Treat Analysis Dataset, which will be comprised of all randomized participants. The primary dataset will be a Modified Intention to Treat Analysis Dataset for all endpoints, comprised of all participants who took at least one dose of study intervention (placebo or treatment), regardless of completeness of follow-up outcome data. The Safety Analysis Dataset will be all participants who took at least one dose of study intervention. The Per Protocol Analysis Dataset will be those patients who took at least 9 doses of study intervention for 9 days of the treatment period (10 days). Analysis will utilize ANOVA unless statistically significant differences in the distribution of baseline characteristics or features of non-normality are detected and relevant, at which point contingency utilization of ANCOVA, logistic regression, or other approaches as appropriate will be implemented. Treatment group level rates will be presented as incidence risk ratios relative to the control (placebo) group with 95% confidence intervals.
Safety endpoints will be evaluated on an individual AE by AE event via the DSMB and utilizing summary statistics during treatment and through duration of follow up. Adverse events will be presented by System Organ Class and will include information on start and stop date, severity, projected relationship, expectedness, and outcome and duration (the latter two after the event is considered to have concluded).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Alanyl-glutamine | Experimental | Drug: Alanyl-glutamineAlanyl-glutamine, 44g, taken by mouth daily for 10 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adult of either gender, 18 years or older, with C. difficile infection (CDI)
- Diarrhea associated with C. difficile positive stool assay
- Within 48 hours of receiving either metronidazole for mild-moderate disease or vancomycin for severe uncomplicated disease
- Admitted in the hospital at the time of enrollment
- Ability to provide informed consent
Key exclusion criteria (15 listed)
- Hypotension or shock
- Megacolon or moderate to severe ileus
- Acute abdomen
- Severe leukocytosis (WBC > 20,000 cells /µL)
- Admission to intensive care unit on enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alanyl-glutamineAlso: alaglnAlanyl-glutamine, 44g, taken by mouth daily for 10 days | Drug | Alanyl-glutamine |
Primary outcome
Number of Participants With Recurrent C. Difficile Infection
Time frame: At day forty
Day 40 clinical failure - clinical failure includes death or CDI recurrence assessed 40 days post randomization or lack of clinical cure
Mortality
Time frame: Up to 6 months after end of treatment
Death from any cause at days 40, 70 and 190
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cirle A. Warren, M.D. principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alanyl-glutamine in people with Clostridium Difficile Infection, run by University of Virginia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Recurrent C. Difficile Infection (time frame: At day forty). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2022.