EczemaEarly Phase 1NCT04019769
Glutamine Supplementation in People With Immune Dysregulation
A Early Phase 1 study testing L-glutamine in people with Eczema and MTOROC1 Signaling, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: Glutamine is an amino acid. People get amino acids from food or from the body s cells. The body needs amino acids to stay healthy. Glutamine might help treat some people with immune system problems like atopic dermatitis. Read more about this study
- Who is it for?
- Ages 5 to 65 years
- Conditions the study is for
- Eczema, MTOROC1 Signaling
- What is being tested?
- L-glutamine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Mar 2020to 1 Jan 2021
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 5 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Individuals must meet all of the following criteria to be eligible for study participation:
- Be 5 to 65 years of age, inclusive.
- Able to provide informed consent.
- Be enrolled on NIAID protocol 10-I-0148 and identified on that protocol as meeting at least one of the following 3 criteria:
- Has active, moderate-to-severe AD (defined as objective SCORAD greater than or equal to 15 or total SCORAD greater than or equal to 25).
- Has a confirmed defect in mTORC1 signaling (based on T cell stimulation assay).
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- Has a confirmed CBM loss-of-function gene mutation (identified by genetic sequencing and verified in vitro by testing patient cells and/or transfection of mutant gene into cell lines).
- Females of childbearing potential must agree to use adequate contraception when engaging in sexual activities that can result in pregnancy, beginning 30 days prior to day 0 through study day 120. Acceptable methods of contraception include the following:
- Continuous hormonal contraception used per label without interruption throughout the above period.
- Male or female condom with spermicide.
- Diaphragm or cervical cap with a spermicide.
- Intrauterine device.
- Be willing to allow storage of biological samples for future research purposes.
Who cannot join
- Individuals meeting any of the following criteria will be excluded from study participation:
- Current, active infection requiring treatment.
- Current treatment with a chemotherapeutic agent.
- Participation in an ongoing research protocol evaluating an investigational agent.
- Treatment with approved prescription medications may be exclusionary, to be determined on a case-by-case basis by the principal investigator.
- Significant liver or kidney disease (serum glutamic oxaloacetic transaminase [SGOT], serum glutamine pyruvic transaminase [SGPT], or alkaline phosphatase >2.5 (SqrRoot) upper limit of normal [ULN], total bilirubin >1.5 (SqrRoot) ULN, or serum creatinine >1.5 (SqrRoot) ULN) in the past 30 days.
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- Persons with an active seizure disorder. For persons with a prior history of seizures, the person should be seizure free for 5 years and not on any anti-seizure medication in order to be enrolled into the study. (Since glutamine is metabolized to glutamate and ammonia, and glutamate is the main excitatory neurotransmitter in the central nervous system, there is a theoretical increased risk of seizures.)
- Allergy to monosodium glutamate.
- Malabsorption.
- Pregnancy.
- Breastfeeding.
- Any condition that, in the opinion of the investigator, contraindicates participation in this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Phase 1 Trial of Glutamine Supplementation in Patients With Immune Dysregulation
Background:
Glutamine is an amino acid. People get amino acids from food or from the body s cells. The body needs amino acids to stay healthy. Glutamine might help treat some people with immune system problems like atopic dermatitis.
Read more
Objective:
To study the safety and effectiveness of glutamine supplements for people with certain immune system problems.
Eligibility:
People ages 5-65 with atopic dermatitis and other immune system problems
Design:
Participants will be screened in another protocol.
Participants will have 8 visits.
Visit 1 includes:
Physical exam
Medical history
Blood and urine tests
Saliva sample
Nutrition assessment
For participants with AD, photographs of the skin
Participants will get a diary to record their symptoms every day during the study. They will record any glutamine side effects and bring the diary to every visit.
Visit 2 is about 1 month after visit 1. Participants will repeat visit 1 tests and get glutamine to take home. It is a powder that can be added to drinks or food. They will take it twice a day for 3 months. They will record their doses in a diary each day and bring the diary to all visits.
Participants will have a phone call 5 days after starting glutamine to discuss how they are feeling.
Visit 3 is about 7 days after participants start taking glutamine. They will have blood tests.
Visits 4, 5, and 6 occur each month participants are taking glutamine. Participants will repeat visit 1 tests.
Participants will stop taking glutamine after visit 6.
Visits 7 and 8 occur 1 and 3 months after participants stop taking glutamine. Participants will repeat visit 1 tests.
Read the detailed description
Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin condition that typically begins in infancy or early childhood and can be highly debilitating with a marked reduction in quality of life. Current treatment modalities for AD include frequent use of skin moisturizers such as creams or emollients, topical corticosteroids and topical calcineurin inhibitors, systemic immunosuppressive drugs, and, in select cases of refractory disease, wet wrap therapy. The available systemic treatments for AD when topical treatment fails can have substantial adverse effects and are not always effective. The search for targeted therapies based on pathway disruptions in patients could present opportunities to provide therapies on a more personalized basis, tailored to the pathogenic pathways.
Based on prior studies, we have demonstrated that supplemental glutamine has potential as an effective AD treatment in patients with caspase activation and recruitment domain (CARD) gene mutations. Prior studies have demonstrated that loss of CARD signaling leads to a decrease in the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. Glutamine supplementation can normalize this defect in mTORC1. The CARD11 BCL10 MALT1 (CBM) signalosome complex is a critical component of mTORC1 activation. Some patients with gene mutations affecting the CBM complex do not develop AD but do develop other symptoms of immunoregulation and may also benefit from glutamine supplementation. We will conduct a phase 1, open-label study to investigate the use of supplemental glutamine in patients with immune dysregulation. Subjects 5 to 65 years of age will take oral glutamine daily for 3 months. To assess the role of the mTORC1 pathway in response to glutamine supplementation, we will enroll 3 groups of patients: 1) those with AD and a defect in mTORC1 signaling or a mutation in the CBM complex; 2) those with AD who do not have a defect in mTORC1 signaling or a mutation in the CBM complex; and 3) those who have a defect in mTORC1 signaling or a mutation in the CBM complex and do not have AD. Subjects will complete a daily symptom diary for 1 month before starting glutamine to document baseline disease status. Disease severity will be assessed at baseline, at the end of glutamine supplementation, and 1 and 3 months after completing the glutamine regimen. Blood will be collected periodically for safety, tolerability, and research assessments.
- Conditions
- Eczema, MTOROC1 Signaling
- Being tested
- L-glutamine
- Keywords
- Eczema, MTORC1 Signaling, CBM Complex
- Medical subject headings
- Eczema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-glutamineDrug
product will be obtained by Endari and administered by NIH pharmacy. Patient will take supplement as prescribed
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | All patients will receive L-glutamine 10-30mg daily based on weight for 3 months Receives: Drug: L-glutamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To characterize the safety and tolerability of glutamine supplementation in patients with immune disregulation.
assess safety and tolerability of glutamine
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2019
- Study start12 Mar 2020 (estimated)
- Primary completion1 Jan 2021 (estimated)
- Study completion1 Jan 2021 (estimated)
Why it stopped: PI left NIH. No subjects enrolled.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EczemaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Joshua D Milner, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04019769
- Sponsor's protocol ID
- 190121
- Other IDs
- 19-I-0121
- Status last verified
- Mar 2020
- First submitted
- 12 Jul 2019
- Last updated
- 16 Mar 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Trial of Glutamine Supplementation in Patients With Immune Dysregulation
- ClinicalTrials.gov ID
- NCT04019769
- Acronym / sponsor ID
- 190121
- Conditions
- Eczema, MTOROC1 Signaling
- Keywords
- Eczema, MTORC1 Signaling, CBM Complex
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI left NIH. No subjects enrolled.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 12 Mar 2020 (estimated)
- Primary completion
- 1 Jan 2021 (estimated)
- Study completion
- 1 Jan 2021 (estimated)
- First posted
- 15 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Glutamine is an amino acid. People get amino acids from food or from the body s cells. The body needs amino acids to stay healthy. Glutamine might help treat some people with immune system problems like atopic dermatitis.
Objective:
To study the safety and effectiveness of glutamine supplements for people with certain immune system problems.
Eligibility:
People ages 5-65 with atopic dermatitis and other immune system problems
Design:
Participants will be screened in another protocol.
Participants will have 8 visits.
Visit 1 includes:
Physical exam
Medical history
Blood and urine tests
Saliva sample
Nutrition assessment
For participants with AD, photographs of the skin
Participants will get a diary to record their symptoms every day during the study. They will record any glutamine side effects and bring the diary to every visit.
Visit 2 is about 1 month after visit 1. Participants will repeat visit 1 tests and get glutamine to take home. It is a powder that can be added to drinks or food. They will take it twice a day for 3 months. They will record their doses in a diary each day and bring the diary to all visits.
Participants will have a phone call 5 days after starting glutamine to discuss how they are feeling.
Visit 3 is about 7 days after participants start taking glutamine. They will have blood tests.
Visits 4, 5, and 6 occur each month participants are taking glutamine. Participants will repeat visit 1 tests.
Participants will stop taking glutamine after visit 6.
Visits 7 and 8 occur 1 and 3 months after participants stop taking glutamine. Participants will repeat visit 1 tests.
Detailed description
Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin condition that typically begins in infancy or early childhood and can be highly debilitating with a marked reduction in quality of life. Current treatment modalities for AD include frequent use of skin moisturizers such as creams or emollients, topical corticosteroids and topical calcineurin inhibitors, systemic immunosuppressive drugs, and, in select cases of refractory disease, wet wrap therapy. The available systemic treatments for AD when topical treatment fails can have substantial adverse effects and are not always effective. The search for targeted therapies based on pathway disruptions in patients could present opportunities to provide therapies on a more personalized basis, tailored to the pathogenic pathways.
Based on prior studies, we have demonstrated that supplemental glutamine has potential as an effective AD treatment in patients with caspase activation and recruitment domain (CARD) gene mutations. Prior studies have demonstrated that loss of CARD signaling leads to a decrease in the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. Glutamine supplementation can normalize this defect in mTORC1. The CARD11 BCL10 MALT1 (CBM) signalosome complex is a critical component of mTORC1 activation. Some patients with gene mutations affecting the CBM complex do not develop AD but do develop other symptoms of immunoregulation and may also benefit from glutamine supplementation. We will conduct a phase 1, open-label study to investigate the use of supplemental glutamine in patients with immune dysregulation. Subjects 5 to 65 years of age will take oral glutamine daily for 3 months. To assess the role of the mTORC1 pathway in response to glutamine supplementation, we will enroll 3 groups of patients: 1) those with AD and a defect in mTORC1 signaling or a mutation in the CBM complex; 2) those with AD who do not have a defect in mTORC1 signaling or a mutation in the CBM complex; and 3) those who have a defect in mTORC1 signaling or a mutation in the CBM complex and do not have AD. Subjects will complete a daily symptom diary for 1 month before starting glutamine to document baseline disease status. Disease severity will be assessed at baseline, at the end of glutamine supplementation, and 1 and 3 months after completing the glutamine regimen. Blood will be collected periodically for safety, tolerability, and research assessments.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: L-glutamineAll patients will receive L-glutamine 10-30mg daily based on weight for 3 months |
Who may qualify
- Ages
- 5 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Individuals must meet all of the following criteria to be eligible for study participation:
- Be 5 to 65 years of age, inclusive.
- Able to provide informed consent.
- Be enrolled on NIAID protocol 10-I-0148 and identified on that protocol as meeting at least one of the following 3 criteria:
- Females of childbearing potential must agree to use adequate contraception when engaging in sexual activities that can result in pregnancy, beginning 30 days prior to day 0 through study day 120. Acceptable methods of contraception include the following:
Key exclusion criteria (12 listed)
- Individuals meeting any of the following criteria will be excluded from study participation:
- Current, active infection requiring treatment.
- Current treatment with a chemotherapeutic agent.
- Participation in an ongoing research protocol evaluating an investigational agent.
- Treatment with approved prescription medications may be exclusionary, to be determined on a case-by-case basis by the principal investigator.
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 |
|---|---|---|
| L-glutamineproduct will be obtained by Endari and administered by NIH pharmacy. Patient will take supplement as prescribed | Drug | 1 |
Primary outcome
To characterize the safety and tolerability of glutamine supplementation in patients with immune disregulation.
Time frame: 1 year
assess safety and tolerability of glutamine
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2020.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Joshua D Milner, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing L-glutamine in people with Eczema and MTOROC1 Signaling, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 13 inclusion and 12 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: withdrawn, as of the sponsor's last update on 16 Mar 2020. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
To characterize the safety and tolerability of glutamine supplementation in patients with immune disregulation. (time frame: 1 year). 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 16 Mar 2020.