AzTrials
AzTrials

XMENPhase 1/2NCT02496676

Magnesium Supplementation in People With XMEN Syndrome

A Phase 1/2 study testing Magnesium L-threonate and Intravenous (IV) magnesium sulfate (MgSO4) in people with XMEN, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Background: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia syndrome is called XMEN syndrome. In this genetic condition, the cells have less magnesium than normal. This makes it hard for the body to fight infections. Read more about this study

Who is it for?
Ages 6 years and older, men only
Conditions the study is for
XMEN
What is being tested?
Magnesium L-threonate and Intravenous (IV) magnesium sulfate (MgSO4)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
8 participants
Where
1 siteUnited States
Study dates
17 May 2016to 23 Apr 2020
Phase
Phase 1/2
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 6 years and older
  • Men only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • All of the following inclusion criteria must be met prior to enrollment:
  • Molecular diagnosis of the MAGT1 genetic defect
  • Greater than or equal to 6 years years of age
  • Willingness to stop magnesium supplements (other than the study agent) and any multivitamins or over-the counter-supplements that may contain magnesium for the duration of the study
  • Willingness to go without magnesium supplementation during a 12-week placebo period and during both 2-week washout periods (pre-study and mid-study)
  • Willingness to have samples stored for future research
  • Must have a physician at home for follow-up care

Who cannot join

  • Chemotherapy or radiotherapy for lymphoma within 12 months prior to enrollment
  • Rituximab exposure within 6 months prior to enrollment
  • Systemic symptoms suggestive of evolving lymphoma
  • History of clinically significant cardiac arrhythmias or cardiac defects
  • Renal insufficiency (calculated creatinine clearance <50 mL/min or insufficiency requiring dialysis)
  • Advanced heart block
Show all 12Show fewer
  • Hypermagnesemia, defined as magnesium serum concentrations >2 mmol/L (>5 mg/dL)
  • Human immunodeficiency virus (HIV) seropositivity
  • Signs or symptoms of life-threatening active microbial infection
  • History of hypersensitivity to any of the study agents
  • Any condition that, in the investigator s opinion, may substantially increase the risk associated with study participation or compromise the study s scientific objectives
  • Participation in a clinical protocol which includes an intervention that, in the opinion of the investigator, may affect the results of the current study

Trial locations and contacts

1 site in 1 country.

United States1 site
  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Double-blind, Placebo-controlled, Crossover Study of Magnesium Supplementation in Patients With XMEN Syndrome

Background:

  • X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia syndrome is called XMEN syndrome. In this genetic condition, the cells have less magnesium than normal. This makes it hard for the body to fight infections. Researchers want to see if magnesium supplements can make it easier for the body to fight infection.
Read more

Objective:

  • To see if magnesium supplements can strengthen the immune system and reduce the amount of Epstein-Barr virus in people with XMEN syndrome.

Eligibility:

  • People ages 6 and older who have XMEN syndrome

Design:

  • Participants will be screened with:
  • Medical history
  • Physical exam
  • CT scan: Participants will drink a contrast and may get dye through an IV in the arm. They will lie in a machine that takes pictures of the body.
  • EKG: Small sticky patches on the body will trace heart rhythm.
  • Blood tests
  • The study has 2 parts.
  • Participants doing both parts will participate for 1 year and visit the clinic about 15 times. These visits will include a physical exam and blood and urine tests.
  • Participants doing only the first part finish in 6 months and have fewer visits.
  • For study part 1, participants will take magnesium pills for 3 months and placebo pills for another 3 months.
  • At 3 and 6 months, they will have physical exam, medical history, blood and urine tests, and an EKG.
  • If the magnesium pills are not helpful, participants will do study part 2.
  • They will be admitted to the hospital for 4 5 days to get magnesium for 3 days through an arm vein.
  • They will take magnesium pills for another 6 months.
Read the detailed description

X-linked immunodeficiency magnesium defect, Epstein-Barr virus (EBV) infection and neoplasia (XMEN) syndrome is a primary immunodeficiency caused by the loss of expression of the magnesium transporter 1 (MAGT1). This syndrome is associated with cluster of differentiation 4 (CD4) lymphopenia, chronic EBV infection in most patients, and EBV-related lymphoproliferative disorders. The loss of MAGT1 leads to impaired T cell activation and decreased expression of the activator receptor, NKG2D on natural killer (NK) cells and CD8 T cells, leading to decreased EBV-specific cytolytic function of these cells. Results of previous studies suggest that magnesium supplementation may be a viable therapeutic option for patients with XMEN.

The proposed study has 2 parts, and patients will be divided into 2 cohorts. Patients in cohort 1 (high EBV group) will have baseline blood EBV viral load greater than or equal to 5,000 copies/mL or EBV log greater than or equal to 3.7 IU/mL. Patients in cohort 2 (low/no EBV group) will have baseline blood EBV viral load <5,000 copies/mL or EBV log <3.7 IU/mL. Part I is a randomized, double-blind, placebo-controlled, crossover study to evaluate the safety and efficacy of oral magnesium L-threonate in patients with XMEN syndrome. Within each cohort, patients will be randomized to receive escalating doses of either placebo or oral magnesium L-threonate for 12 weeks. Patients will then receive the crossover treatment (magnesium or placebo) for an additional 12 weeks. For patients who experience a 0.5-log decrease in the number of EBV-infected B cells (cohort 1) or a greater than or equal to 2-fold increase in NKG2D receptor expression on cluster of differentiation 8 (CD8+) T cells (cohort 2) with oral magnesium as compared to placebo, the study will be complete. Patients who do not meet this efficacy outcome will undergo a 2-week washout period and proceed to Part II, an open-label, non-randomized evaluation of intravenous magnesium sulfate (MgSO4) followed by oral magnesium L-threonate. These patients will be hospitalized to receive 3 days of intravenous MgSO4 in 3 daily doses totaling 30 mg/kg/day. They will then restart escalating doses of oral magnesium L-threonate and continue for the remaining 24 weeks of Part II. If conducted, Part II will allow for secondary analyses to compare different durations of magnesium supplementation.

Conditions
XMEN
Being tested
Magnesium L-threonate, Placebo, Intravenous (IV) magnesium sulfate (MgSO4)
Keywords
Neoplasia, magnesium transporter 1 (MAGT1), Primary Immunodeficiency, X-linked immunodeficiency, Epstein-Barr virus (EBV) infection
Medical subject headings
Neoplasms, Primary Immunodeficiency Diseases, Epstein-Barr Virus Infections, Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Magnesium L-threonateDietary supplement

    In Part I, participants will receive 12 weeks of oral magnesium L-threonate; will be dose escalated based on weight.

    In Part 2, participants will receive 24 weeks of oral magnesium L-threonate; will be dose escalated based on weight.

  • PlaceboOther

    In Part I, participants will receive 12 weeks of oral placebo; will be dose escalated based on weight.

  • Intravenous (IV) magnesium sulfate (MgSO4)Drug

    In Part II, participants will be hospitalized to receive 3 days of IV magnesium sulfate (MgS04).

Study groups in NCT02496676
Study groupRoleWhat they receive
Magnesium, then placeboActive comparatorIn phase 1, participants received oral magnesium L-threonate for 12 weeks then crossover to placebo for 12 weeks, followed by a 2-week washout period. In phase 2, all participants received 3 days of intravenous MgSO4 in 3 daily doses totaling 30 mg/kg/day followed by oral magnesium L-threonate for 24 weeks.
Receives: Dietary Supplement: Magnesium L-threonate; Other: Placebo; Drug: Intravenous (IV) magnesium sulfate (MgSO4)
Placebo, then magnesiumPlacebo comparatorIn phase 1, participants received oral placebo for 12 weeks then crossover to oral magnesium L-threonate for 12 weeks, followed by a 2-week washout period. In phase 2, all participants received 3 days of intravenous MgSO4 in 3 daily doses totaling 30 mg/kg/day followed by oral magnesium L-threonate for 24 weeks.
Receives: Dietary Supplement: Magnesium L-threonate; Other: Placebo; Drug: Intravenous (IV) magnesium sulfate (MgSO4)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Participants With a ≥0.5 Log Reduction in the Number of EBV-infected B Cells After Magnesium Supplementation as Compared to Placebo - Phase 1

    Participants with a ≥ 0.5 log decrease in the absolute number of Epstein-Barr virus (EBV) infected B-cells by flow cytometric Fluorescence in situ hybridization (FISH) assay after 12 weeks of oral magnesium supplementation compared to 12 weeks of placebo.

    Measured: After 12 weeks of each intervention

  2. Participants With 2-fold or Greater Increase in NKG2D Expression in CD8 T+ Cells After Magnesium Supplementation as Compared to Placebo - Phase 1

    Participants with difference of a 2-fold or greater increase in NKG2D expression in cluster of differentiation 8 (CD8+) T cells after 12 weeks of oral magnesium supplementation versus 12 weeks of placebo.

    Measured: After 12 weeks of each intervention

Secondary outcomes (5)
  1. Participants With 2-fold or Greater Increase in NKG2D Expression in CD8 T+ Cells After Magnesium Supplementation as Compared to Placebo - Phase 1

    Participants with difference of a 2-fold or greater increase in NKG2D expression in cluster of differentiation 8 (CD8+) T cells after 12 weeks of oral magnesium supplementation versus 12 weeks of placebo.

    Measured: After 12 weeks of each intervention

  2. Participants With a Decrease in the Absolute Number of EBV Infected B Cells Before and After Magnesium Supplementation - Phase 2

    Participants with a ≥ 0.5 log decrease in the absolute number of Epstein-Barr virus (EBV) infected B-cells by flow cytometric Fluorescence in situ hybridization (FISH) assay before and after 24 weeks of magnesium supplementation

    Measured: 24 weeks, during phase 2 of study

  3. Participants With 2-fold or Greater Increase in NKG2D Expression in CD8 T+ Cells Before and After Magnesium Supplementation - Phase 2

    Participants with a 2-fold or greater increase in NKG2D expression in CD8+ T cells before and after magnesium supplementation for 24 weeks in phase 2 of study

    Measured: 24 weeks, during phase 2 of study

  4. Participants With Adverse Events by Grade

    Participants with adverse events by grade using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 4) grading criteria.

    • Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; no intervention indicated
    • Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL)
    • Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL
    • Grade 4 Life-threatening consequences; urgent intervention indicated
    • Grade 5 Death related to adverse event (AE)

    Measured: 1 year

  5. Participants With Severe Adverse Events

    Participants with severe adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 4) to evaluate severity.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jul 2015 (estimated)
  2. Study start17 May 2016
  3. Primary completion23 Apr 2020
  4. Study completion23 Apr 2020

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02496676
Sponsor's protocol ID
150161
Other IDs
15-I-0161
Status last verified
Apr 2020
First submitted
9 Jul 2015
Last updated
2 Mar 2022
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Li FY, Chaigne-Delalande B, Kanellopoulou C, Davis JC, Matthews HF, Douek DC, Cohen JI, Uzel G, Su HC, Lenardo MJ. Second messenger role for Mg2+ revealed by human T-cell immunodeficiency. Nature. 2011 Jul 27;475(7357):471-6. doi: 10.1038/nature10246.

    PubMed 21796205
  • Chaigne-Delalande B, Li FY, O'Connor GM, Lukacs MJ, Jiang P, Zheng L, Shatzer A, Biancalana M, Pittaluga S, Matthews HF, Jancel TJ, Bleesing JJ, Marsh RA, Kuijpers TW, Nichols KE, Lucas CL, Nagpal S, Mehmet H, Su HC, Cohen JI, Uzel G, Lenardo MJ. Mg2+ regulates cytotoxic functions of NK and CD8 T cells in chronic EBV infection through NKG2D. Science. 2013 Jul 12;341(6142):186-91. doi: 10.1126/science.1240094.

    PubMed 23846901
  • Li FY, Chaigne-Delalande B, Su H, Uzel G, Matthews H, Lenardo MJ. XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus. Blood. 2014 Apr 3;123(14):2148-52. doi: 10.1182/blood-2013-11-538686. Epub 2014 Feb 18.

    PubMed 24550228
  • Chauvin SD, Price S, Zou J, Hunsberger S, Brofferio A, Matthews H, Similuk M, Rosenzweig SD, Su HC, Cohen JI, Lenardo MJ, Ravell JC. A Double-Blind, Placebo-Controlled, Crossover Study of Magnesium Supplementation in Patients with XMEN Disease. J Clin Immunol. 2022 Jan;42(1):108-118. doi: 10.1007/s10875-021-01137-w. Epub 2021 Oct 16.

    PubMed 34655400

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Magnesium L-threonate and Intravenous (IV) magnesium sulfate (MgSO4) in people with XMEN, 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 7 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: finished, as of the sponsor's last update on 2 Mar 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 26 Jan 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?

Participants With a ≥0.5 Log Reduction in the Number of EBV-infected B Cells After Magnesium Supplementation as Compared to Placebo - Phase 1 (time frame: After 12 weeks of each intervention). 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?

On the ClinicalTrials.gov record for NCT02496676, which also lists 4 linked publications.

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 2 Mar 2022.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in