Ca-Mg Butyrate for Gulf War Syndrome

(Butyrate Trial)

Recruiting at 3 trial locations

Overseen By Jonathan Skupsky

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must not be taking: Steroids, Antibiotics, Immunosuppressives, others

Disqualifiers: Schizophrenia, Bipolar, Organ failure, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 18 weeks

120 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that affect gut motility, immune function, or contain calcium or magnesium butyrate at least 3 months before starting. If you're on steroids, antibiotics, or immunosuppressives, you need to stop them at least 1 month prior. Check with the trial team for specific guidance on your medications.

What data supports the effectiveness of the drug Ca-Mg Butyrate for Gulf War Syndrome?

There is some evidence that magnesium, a component of Ca-Mg Butyrate, may help with asthma symptoms, as seen in studies where magnesium improved symptom scores in asthma patients. Additionally, magnesium has shown effectiveness in reducing symptoms of seasonal allergic rhinitis, which suggests it might have potential benefits for other conditions involving inflammation or immune response. ^{1 2 3 4 5}

Is Ca-Mg Butyrate safe for humans?

Research on calcium and magnesium supplements shows they are generally well-tolerated in humans, with no significant adverse effects reported in studies, except for potential mild gastrointestinal issues like diarrhea at high magnesium doses. ^{2 4 6 7 8}

How does the drug Ca-Mg Butyrate differ from other treatments for Gulf War Syndrome?

Ca-Mg Butyrate is unique because it combines calcium and magnesium derivatives with butyric acid, which may offer benefits not seen in other treatments. While magnesium has been studied for its bioavailability and potential neuroprotective effects, the combination with butyric acid in this drug could provide a novel approach to addressing symptoms of Gulf War Syndrome. ^{7 9 10 11 12}

What is the purpose of this trial?

The primary objective of this clinical trial is to determine if treatment with Butyrate formulation that consists of butyric acid as calcium and magnesium derivatives (Ca-Mg Butyrate) improves the physical function of men and women Veterans suffering from Gulf War Illness (GWI). The primary outcome measure is a change from baseline on the Short Form Health Survey 36-item (VSF-36), with respect to physical functioning and symptoms. The secondary outcome will focus on the drug's role in (a) restoring gut microbiome and virome, (b) decreasing gastrointestinal disturbances (constipation, diarrhea, pain), (c) decreasing chronic fatigue, (d) decreasing systemic inflammation, and (e) a decrease in cognitive deficits.

Research Team

Saurabh Chatterjee, PhD

Principal Investigator

VA Long Beach Healthcare System, Long Beach, CA

Eligibility Criteria

This trial is for Gulf War era veterans aged between 40 and 70 who suffer from moderate to severe GWI, as defined by CDC and Kansas criteria. Participants must score less than 30 on the VSF36 physical domain, with no other health conditions that could explain their symptoms.

Inclusion Criteria

I am a Gulf War veteran aged 40-70, in good health before 1990, with symptoms fitting GWI without other explanations.

Exclusion Criteria

Pregnancy or planned pregnancy in the next 6 months

I have a diagnosed inflammatory disorder.

I am taking supplements for gut health or immune support.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive microencapsulated butyrate capsules (600 mg twice a day) or placebo for 18 weeks

18 weeks

Regular visits as per trial protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Virtual visits

Treatment Details

Interventions

• Ca-Mg Butyrate
• Placebo

Trial Overview The trial tests if Ca-Mg Butyrate improves physical function in those with GWI. It measures changes in physical functioning via the VSF-36 survey and examines effects on gut microbiome, gastrointestinal issues, chronic fatigue, inflammation, and cognitive deficits.

Participant Groups

Group I: Cal-Mag-Butyrate Experimental Treatment 1 Intervention

Take oral capsule as directed (600 mg, twice a day for 18 weeks) with or without food.

Group II: Placebo for Cal-Mag-Butyrate Placebo Group 1 Intervention

Take oral capsule as directed (600 mg, twice a day for 18 weeks) with or without food.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Miami VA Healthcare System

Collaborator

Trials

18

Recruited

2,400+

VA Salt Lake City Health Care System

Collaborator

Trials

25

Recruited

262,000+

Findings from Research

Oral magnesium supplements showed a significant improvement in FEV1 (forced expiratory volume in one second) at 8 weeks in a study involving 917 patients with mild to moderate asthma, but no improvements were observed at other follow-up periods or in other asthma-related outcomes.

Despite the initial positive effect on lung function, the overall evidence does not support the use of oral magnesium as an effective adjunct treatment for asthma, as it did not significantly impact other measures like FVC, bronchodilator use, or symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of oral magnesium supplements for the management of stable bronchial asthma: a systematic review and meta-analysis. Abuabat, F., AlAlwan, A., Masuadi, E., et al.[2020]

In a study involving 12 atopic subjects, inhaled NAAGA (60 mg three times daily for one week) did not provide any protective effect against allergen-induced bronchoconstriction compared to a placebo.

The treatment was well tolerated, with no adverse effects reported, indicating a good safety profile despite its lack of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of an inhaled mast cell stabiliser, N-acetyl-aspartyl-glutamate (Zy15109) on allergen-induced immediate bronchoconstriction. Lai, CK., Gregory, J., Holgate, ST.[2019]

In a study of 55 African-American patients with asthma, it was found that they had significantly lower levels of ionized magnesium compared to a control group, suggesting a potential deficiency that could impact asthma management.

All patients with abnormal levels of divalent ions had their levels corrected with intravenous magnesium, indicating that magnesium therapy may be beneficial for certain asthmatic patients with these deficiencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ionized magnesium levels and the ratio of ionized calcium to magnesium in asthma patients before and after treatment with magnesium. Sinert, R., Spektor, M., Gorlin, A., et al.[2013]

In a randomized double-blind study involving 38 participants with seasonal allergic rhinitis, oral magnesium pidolate (MAG2) significantly reduced symptoms such as rhinorrhea, sneezing, and lacrimation compared to placebo, with a high level of statistical significance (P < 0.001).

The study suggests that magnesium's calcium-modulating and antihistamine-like properties may contribute to its effectiveness in alleviating hay fever symptoms, indicating a potential new treatment option for allergic rhinitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnesium pidolate in the treatment of seasonal allergic rhinitis. Preliminary data. Cipolla, C., Occhionero, T., Orciari, P., et al.[2016]

In a study involving 17 asthmatic subjects, short-term magnesium supplementation (400 mg/day) significantly improved asthma symptom scores compared to a placebo, indicating potential benefits for clinical control of asthma.

Despite the improvement in symptom scores, there were no significant changes in objective measures of lung function, such as forced expiratory volume (FEV1) or airway reactivity, suggesting that while magnesium may help with symptoms, it does not necessarily enhance overall lung function in stable asthmatic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigation of the effect of short-term change in dietary magnesium intake in asthma. Hill, J., Micklewright, A., Lewis, S., et al.[2019]

In a Phase I trial involving 698 healthy adults with high-normal diastolic blood pressure, supplementation with calcium and magnesium did not significantly lower blood pressure after 3 and 6 months, indicating these supplements are unlikely to be effective for this purpose.

Subgroup analyses suggested a potential benefit of calcium supplementation in white women, particularly those with lower initial urinary calcium levels, but further research is needed to confirm this finding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of blood pressure effect with calcium and magnesium supplementation in adults with high-normal blood pressure. Results from Phase I of the Trials of Hypertension Prevention (TOHP). Trials of Hypertension Prevention (TOHP) Collaborative Research Group. Yamamoto, ME., Applegate, WB., Klag, MJ., et al.[2022]

In a study involving 17 patients with mild to moderate hypertension, treatment with magnesium aspartate did not lead to a reduction in blood pressure compared to placebo, despite increasing plasma magnesium levels.

The magnesium aspartate was well tolerated without causing side effects like diarrhea, but the findings suggest that dietary magnesium may not play a significant role in managing high blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of effect of oral magnesium on high blood pressure: a double blind study. Cappuccio, FP., Markandu, ND., Beynon, GW., et al.[2019]

Recent evidence from 10 studies, including 5 meta-analyses and 5 randomized controlled trials, suggests that magnesium (Mg) supplementation above the current tolerable upper intake level (UL) of 350 mg/d does not significantly increase the risk of diarrhea in adults.

The analysis indicates that higher doses of magnesium (up to 1200 mg/d) can be safely consumed without major gastrointestinal adverse events, supporting the idea that the UL for magnesium should be re-evaluated to potentially allow for greater supplementation and reduce undernutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspective: Call for Re-evaluation of the Tolerable Upper Intake Level for Magnesium Supplementation in Adults. Costello, R., Rosanoff, A., Nielsen, F., et al.[2023]

In a study involving 46 healthy individuals over 60 days, magnesium citrate and amino-acid chelate showed significantly better absorption compared to magnesium oxide, indicating they are more effective forms of magnesium supplementation.

Magnesium citrate not only resulted in the highest serum magnesium levels after both acute and chronic supplementation but also led to the greatest salivary magnesium concentration, suggesting it has superior bioavailability for enhancing magnesium levels in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study. Walker, AF., Marakis, G., Christie, S., et al.[2022]

In a study involving normal and excitotoxically affected rats, a single injection of magnesium sulfate significantly increased serum magnesium levels, but did not change magnesium levels in the hippocampus unless the brain was perfused before measurement.

After excitotoxic treatment with glutamate analogues, magnesium levels in the unaffected side of the brain increased by up to 38%, suggesting that magnesium could be a potential therapeutic agent to protect against excitotoxic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quinolinate and kainate facilitate magnesium penetration into brain tissue. Rothe, F., Wolf, G., Fischer, S., et al.[2019]

In a study involving 280 rats on a magnesium-deficient diet, magnesium L-aspartate was found to be the most effective and fastest at compensating for magnesium deficiency compared to 19 other magnesium salts.

Magnesium chloride also showed high efficiency among inorganic salts, and both magnesium chloride and magnesium L-aspartate combined with vitamin B6 significantly improved magnesium levels in the rats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparative study of magnesium salts bioavailability in rats fed a magnesium-deficient diet]. Spasov, AA., Petrov, VI., Iezhitsa, IN., et al.[2016]

Magnesium chloride (MgCl(2)) therapy significantly improves cognitive function and sensorimotor performance in rats following traumatic brain injury, with a dose-dependent effect observed in recovery.

Higher doses of MgCl(2) (2 mmol/kg) led to notable improvements in memory tests and sensorimotor tasks, indicating its potential as a therapeutic intervention for cognitive impairments after brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The behavioral effects of magnesium therapy on recovery of function following bilateral anterior medial cortex lesions in the rat. Hoane, MR., Knotts, AA., Akstulewicz, SL., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

The role of oral magnesium supplements for the management of stable bronchial asthma: a systematic review and meta-analysis. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Effect of an inhaled mast cell stabiliser, N-acetyl-aspartyl-glutamate (Zy15109) on allergen-induced immediate bronchoconstriction. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Ionized magnesium levels and the ratio of ionized calcium to magnesium in asthma patients before and after treatment with magnesium. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Magnesium pidolate in the treatment of seasonal allergic rhinitis. Preliminary data. [2016]

5. England pubmed.ncbi.nlm.nih.gov

Investigation of the effect of short-term change in dietary magnesium intake in asthma. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Lack of blood pressure effect with calcium and magnesium supplementation in adults with high-normal blood pressure. Results from Phase I of the Trials of Hypertension Prevention (TOHP). Trials of Hypertension Prevention (TOHP) Collaborative Research Group. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Lack of effect of oral magnesium on high blood pressure: a double blind study. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Perspective: Call for Re-evaluation of the Tolerable Upper Intake Level for Magnesium Supplementation in Adults. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Quinolinate and kainate facilitate magnesium penetration into brain tissue. [2019]

11. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Comparative study of magnesium salts bioavailability in rats fed a magnesium-deficient diet]. [2016]

12. United States pubmed.ncbi.nlm.nih.gov

The behavioral effects of magnesium therapy on recovery of function following bilateral anterior medial cortex lesions in the rat. [2019]