Trial Outcomes & Findings for Magnesium Supplementation in People With XMEN Syndrome (NCT NCT02496676)
NCT ID: NCT02496676
Last Updated: 2022-03-02
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
8 participants
Primary outcome timeframe
After 12 weeks of each intervention
Results posted on
2022-03-02
Participant Flow
8 participants were consented to protocol. 2 participants did not meet inclusion criteria and one participant declined to participate.
Participant milestones
| Measure |
Magnesium, Then Placebo
In 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.
|
Placebo, Then Magnesium
In 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.
|
|---|---|---|
|
Phase 1 - Period 1
STARTED
|
2
|
3
|
|
Phase 1 - Period 1
COMPLETED
|
2
|
2
|
|
Phase 1 - Period 1
NOT COMPLETED
|
0
|
1
|
|
Phase 1 - Period 2
STARTED
|
2
|
2
|
|
Phase 1 - Period 2
COMPLETED
|
2
|
2
|
|
Phase 1 - Period 2
NOT COMPLETED
|
0
|
0
|
|
Washout Period
STARTED
|
2
|
2
|
|
Washout Period
COMPLETED
|
2
|
2
|
|
Washout Period
NOT COMPLETED
|
0
|
0
|
|
Phase 2 - IV MgSO4
STARTED
|
2
|
2
|
|
Phase 2 - IV MgSO4
COMPLETED
|
2
|
1
|
|
Phase 2 - IV MgSO4
NOT COMPLETED
|
0
|
1
|
|
Phase 2 - Oral Magnesium
STARTED
|
2
|
1
|
|
Phase 2 - Oral Magnesium
COMPLETED
|
2
|
1
|
|
Phase 2 - Oral Magnesium
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Magnesium, Then Placebo
In 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.
|
Placebo, Then Magnesium
In 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.
|
|---|---|---|
|
Phase 1 - Period 1
Adverse Event
|
0
|
1
|
|
Phase 2 - IV MgSO4
Adverse Event
|
0
|
1
|
Baseline Characteristics
Magnesium Supplementation in People With XMEN Syndrome
Baseline characteristics by cohort
| Measure |
Magnesium, Then Placebo
n=2 Participants
In 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.
|
Placebo, Then Magnesium
n=3 Participants
In 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.
|
Total
n=5 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: After 12 weeks of each interventionPopulation: The analyses included only EBV positive subject who completed Phase 1 of the study. In this phase, two participants were EBV positive, but only one participant completed 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.
Outcome measures
| Measure |
Phase 2 - IV MgSO4
In phase 2, participants received 3 days of intravenous MgSO4 in 3 daily doses totaling 30 mg/kg/day
|
Phase 2 - Oral Magnesium
In phase 2, participants received oral magnesium L-threonate for 24 weeks
|
Magnesium
n=1 Participants
Participants received oral magnesium L-threonate for 12 weeks
|
Placebo
n=1 Participants
Participants received oral placebo for 12 weeks
|
|---|---|---|---|---|
|
Participants With a ≥0.5 Log Reduction in the Number of EBV-infected B Cells After Magnesium Supplementation as Compared to Placebo - Phase 1
|
—
|
—
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: After 12 weeks of each interventionPopulation: The analyses included only EBV negative subjects who completed phase 1 of the study, which is the crossover phase.
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.
Outcome measures
| Measure |
Phase 2 - IV MgSO4
In phase 2, participants received 3 days of intravenous MgSO4 in 3 daily doses totaling 30 mg/kg/day
|
Phase 2 - Oral Magnesium
In phase 2, participants received oral magnesium L-threonate for 24 weeks
|
Magnesium
n=3 Participants
Participants received oral magnesium L-threonate for 12 weeks
|
Placebo
n=3 Participants
Participants received oral placebo for 12 weeks
|
|---|---|---|---|---|
|
Participants With 2-fold or Greater Increase in NKG2D Expression in CD8 T+ Cells After Magnesium Supplementation as Compared to Placebo - Phase 1
|
—
|
—
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: After 12 weeks of each interventionPopulation: The analyses included only EBV positive subject who completed Phase 1 of the study. In this phase, two participants were EBV positive, but only one participant completed 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.
Outcome measures
| Measure |
Phase 2 - IV MgSO4
In phase 2, participants received 3 days of intravenous MgSO4 in 3 daily doses totaling 30 mg/kg/day
|
Phase 2 - Oral Magnesium
In phase 2, participants received oral magnesium L-threonate for 24 weeks
|
Magnesium
n=1 Participants
Participants received oral magnesium L-threonate for 12 weeks
|
Placebo
n=1 Participants
Participants received oral placebo for 12 weeks
|
|---|---|---|---|---|
|
Participants With 2-fold or Greater Increase in NKG2D Expression in CD8 T+ Cells After Magnesium Supplementation as Compared to Placebo - Phase 1
|
—
|
—
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 24 weeks, during phase 2 of studyPopulation: Analysis included all EBV positive participants who completed phase 2 of study
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
Outcome measures
| Measure |
Phase 2 - IV MgSO4
In phase 2, participants received 3 days of intravenous MgSO4 in 3 daily doses totaling 30 mg/kg/day
|
Phase 2 - Oral Magnesium
In phase 2, participants received oral magnesium L-threonate for 24 weeks
|
Magnesium
n=1 Participants
Participants received oral magnesium L-threonate for 12 weeks
|
Placebo
Participants received oral placebo for 12 weeks
|
|---|---|---|---|---|
|
Participants With a Decrease in the Absolute Number of EBV Infected B Cells Before and After Magnesium Supplementation - Phase 2
|
—
|
—
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: 24 weeks, during phase 2 of studyPopulation: Analysis included all participants who completed phase 2 of study
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
Outcome measures
| Measure |
Phase 2 - IV MgSO4
In phase 2, participants received 3 days of intravenous MgSO4 in 3 daily doses totaling 30 mg/kg/day
|
Phase 2 - Oral Magnesium
In phase 2, participants received oral magnesium L-threonate for 24 weeks
|
Magnesium
n=3 Participants
Participants received oral magnesium L-threonate for 12 weeks
|
Placebo
Participants received oral placebo for 12 weeks
|
|---|---|---|---|---|
|
Participants With 2-fold or Greater Increase in NKG2D Expression in CD8 T+ Cells Before and After Magnesium Supplementation - Phase 2
|
—
|
—
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: 1 yearPopulation: Analysis included all subjects who started each arm of the study
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)
Outcome measures
| Measure |
Phase 2 - IV MgSO4
n=4 Participants
In phase 2, participants received 3 days of intravenous MgSO4 in 3 daily doses totaling 30 mg/kg/day
|
Phase 2 - Oral Magnesium
n=3 Participants
In phase 2, participants received oral magnesium L-threonate for 24 weeks
|
Magnesium
n=4 Participants
Participants received oral magnesium L-threonate for 12 weeks
|
Placebo
n=5 Participants
Participants received oral placebo for 12 weeks
|
|---|---|---|---|---|
|
Participants With Adverse Events by Grade
Grade 1
|
1 Participants
|
2 Participants
|
4 Participants
|
4 Participants
|
|
Participants With Adverse Events by Grade
Grade 2
|
1 Participants
|
3 Participants
|
1 Participants
|
3 Participants
|
|
Participants With Adverse Events by Grade
Grade 3
|
1 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Participants With Adverse Events by Grade
Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants With Adverse Events by Grade
Grade 5
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 1 yearPopulation: Analysis included all subjects who started each arm of the study
Participants with severe adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 4) to evaluate severity.
Outcome measures
| Measure |
Phase 2 - IV MgSO4
n=4 Participants
In phase 2, participants received 3 days of intravenous MgSO4 in 3 daily doses totaling 30 mg/kg/day
|
Phase 2 - Oral Magnesium
n=3 Participants
In phase 2, participants received oral magnesium L-threonate for 24 weeks
|
Magnesium
n=4 Participants
Participants received oral magnesium L-threonate for 12 weeks
|
Placebo
n=5 Participants
Participants received oral placebo for 12 weeks
|
|---|---|---|---|---|
|
Participants With Severe Adverse Events
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Phase 1 - Oral Magnesium
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Phase 1 - Placebo
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Phase 2 - IV MgSO4
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Phase 2 - Oral Magnesium
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Phase 1 - Oral Magnesium
n=4 participants at risk
In phase 1, participants received oral magnesium L-threonate for 12 weeks
|
Phase 1 - Placebo
n=5 participants at risk
Participants received oral placebo for 12 weeks
|
Phase 2 - IV MgSO4
n=4 participants at risk
In phase 2, participants received 3 days of intravenous MgSO4 in 3 daily doses totaling 30 mg/kg/day
|
Phase 2 - Oral Magnesium
n=3 participants at risk
In phase 2, participants received oral magnesium L-threonate for 24 weeks
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Increased tendency to bruise
|
25.0%
1/4 • Number of events 1 • 1 year
|
0.00%
0/5 • 1 year
|
0.00%
0/4 • 1 year
|
0.00%
0/3 • 1 year
|
|
Blood and lymphatic system disorders
Lymphadenitis
|
0.00%
0/4 • 1 year
|
0.00%
0/5 • 1 year
|
0.00%
0/4 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
Cardiac disorders
Dizziness
|
0.00%
0/4 • 1 year
|
20.0%
1/5 • Number of events 1 • 1 year
|
0.00%
0/4 • 1 year
|
0.00%
0/3 • 1 year
|
|
Ear and labyrinth disorders
Otitis media
|
25.0%
1/4 • Number of events 1 • 1 year
|
0.00%
0/5 • 1 year
|
0.00%
0/4 • 1 year
|
0.00%
0/3 • 1 year
|
|
Gastrointestinal disorders
Abdominal pain
|
75.0%
3/4 • Number of events 4 • 1 year
|
60.0%
3/5 • Number of events 8 • 1 year
|
0.00%
0/4 • 1 year
|
0.00%
0/3 • 1 year
|
|
Gastrointestinal disorders
Diarrhoea
|
25.0%
1/4 • Number of events 1 • 1 year
|
60.0%
3/5 • Number of events 3 • 1 year
|
0.00%
0/4 • 1 year
|
33.3%
1/3 • Number of events 5 • 1 year
|
|
Gastrointestinal disorders
Dyspepsia
|
25.0%
1/4 • Number of events 1 • 1 year
|
0.00%
0/5 • 1 year
|
0.00%
0/4 • 1 year
|
0.00%
0/3 • 1 year
|
|
Gastrointestinal disorders
Hiccups
|
25.0%
1/4 • Number of events 1 • 1 year
|
0.00%
0/5 • 1 year
|
0.00%
0/4 • 1 year
|
0.00%
0/3 • 1 year
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.00%
0/4 • 1 year
|
0.00%
0/5 • 1 year
|
0.00%
0/4 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
25.0%
1/4 • Number of events 1 • 1 year
|
0.00%
0/5 • 1 year
|
0.00%
0/4 • 1 year
|
0.00%
0/3 • 1 year
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/4 • 1 year
|
20.0%
1/5 • Number of events 1 • 1 year
|
0.00%
0/4 • 1 year
|
0.00%
0/3 • 1 year
|
|
General disorders
Fatigue
|
25.0%
1/4 • Number of events 2 • 1 year
|
0.00%
0/5 • 1 year
|
0.00%
0/4 • 1 year
|
0.00%
0/3 • 1 year
|
|
General disorders
Pain
|
25.0%
1/4 • Number of events 1 • 1 year
|
0.00%
0/5 • 1 year
|
0.00%
0/4 • 1 year
|
0.00%
0/3 • 1 year
|
|
Infections and infestations
Acute sinusitis
|
0.00%
0/4 • 1 year
|
0.00%
0/5 • 1 year
|
0.00%
0/4 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
Infections and infestations
Skin infection
|
0.00%
0/4 • 1 year
|
0.00%
0/5 • 1 year
|
0.00%
0/4 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
Investigations
Alanine aminotransferase increased
|
25.0%
1/4 • Number of events 1 • 1 year
|
0.00%
0/5 • 1 year
|
25.0%
1/4 • Number of events 2 • 1 year
|
66.7%
2/3 • Number of events 2 • 1 year
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/4 • 1 year
|
0.00%
0/5 • 1 year
|
25.0%
1/4 • Number of events 1 • 1 year
|
33.3%
1/3 • Number of events 2 • 1 year
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/4 • 1 year
|
0.00%
0/5 • 1 year
|
0.00%
0/4 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
Investigations
White blood cell count increased
|
25.0%
1/4 • Number of events 1 • 1 year
|
0.00%
0/5 • 1 year
|
0.00%
0/4 • 1 year
|
0.00%
0/3 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
25.0%
1/4 • Number of events 1 • 1 year
|
0.00%
0/5 • 1 year
|
0.00%
0/4 • 1 year
|
0.00%
0/3 • 1 year
|
|
Nervous system disorders
Headache
|
50.0%
2/4 • Number of events 13 • 1 year
|
60.0%
3/5 • Number of events 14 • 1 year
|
0.00%
0/4 • 1 year
|
33.3%
1/3 • Number of events 2 • 1 year
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/4 • 1 year
|
20.0%
1/5 • Number of events 1 • 1 year
|
0.00%
0/4 • 1 year
|
0.00%
0/3 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
50.0%
2/4 • Number of events 2 • 1 year
|
0.00%
0/5 • 1 year
|
0.00%
0/4 • 1 year
|
0.00%
0/3 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/4 • 1 year
|
20.0%
1/5 • Number of events 1 • 1 year
|
0.00%
0/4 • 1 year
|
0.00%
0/3 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/4 • 1 year
|
20.0%
1/5 • Number of events 1 • 1 year
|
0.00%
0/4 • 1 year
|
0.00%
0/3 • 1 year
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
25.0%
1/4 • Number of events 1 • 1 year
|
0.00%
0/5 • 1 year
|
0.00%
0/4 • 1 year
|
0.00%
0/3 • 1 year
|
Additional Information
Ravell Aumaitre, Juan
National Institute of Allergy and Infectious Diseases
Phone: +1 301 761 6669
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place