Magnesium Sulfate for Mesothelioma

(MAGIC-AKI Trial)

Overseen By Shruti Gupta, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Disqualifiers: Kidney disease, Neuromuscular disease, Coronary artery disease, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether high doses of magnesium sulfate can prevent kidney issues in people with mesothelioma, a type of cancer, undergoing surgery with a specific chemotherapy treatment (HIOC with cisplatin). Participants will receive either magnesium sulfate (also known as Epsom salt) or a placebo (a substance with no active treatment) to determine if magnesium can protect the kidneys during treatment. Eligible participants are adults with malignant mesothelioma undergoing surgery with chemotherapy. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer care.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are participating in another study with an experimental therapy that might interact with IV magnesium, you may not be eligible.

Is there any evidence suggesting that magnesium sulfate is likely to be safe for humans?

Research has shown that magnesium sulfate is generally safe. The FDA has approved it as a food additive, indicating its safety in foods. Studies also confirm its safety in cosmetics.

For medical use, patients have tolerated different doses of magnesium sulfate well. Specifically, testing in people with mesothelioma undergoing a particular chemotherapy treatment revealed no serious safety issues.

Overall, previous research reports that magnesium sulfate is well-tolerated, with no major side effects. However, safety can vary, so discussing any concerns with a healthcare provider is advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for mesothelioma?

Unlike the standard treatments for mesothelioma, which often involve chemotherapy, surgery, and radiation, magnesium sulfate offers a novel approach by aiming to stabilize patients during anesthesia and potentially improve surgical outcomes. Researchers are excited about magnesium sulfate because it uses magnesium as an active ingredient, administered intravenously, which might help manage the body's response to surgery more effectively. This method could lead to more consistent magnesium levels in the blood, optimizing recovery and potentially enhancing the effectiveness of other treatments.

What evidence suggests that magnesium sulfate might be an effective treatment for mesothelioma?

This trial will compare Magnesium Sulfate with a placebo (Normal Saline) to evaluate its potential benefits for patients with mesothelioma undergoing chemotherapy with cisplatin. Research suggests that magnesium sulfate might protect the kidneys during chemotherapy. One study showed that kidney problems were similar in patients who received magnesium and those who did not. However, magnesium plays a crucial role in many body functions and might help manage chemotherapy side effects. While researchers continue to study the exact benefits of magnesium sulfate, its role in balancing minerals in the body could be helpful. More evidence is needed to confirm its protective effects during chemotherapy. ^{1 2 4 6 7}

Who Is on the Research Team?

Shruti Gupta, MD, MPH

Principal Investigator

Brigham and Women's Hospital

David E. Leaf, MD, MMSc

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for adults with malignant mesothelioma who are undergoing surgery with HIOC. Participants must be treated by Dr. Raphael Bueno or another BWH thoracic surgeon and have normal kidney function. It's not for those with slow heart rates, recent COVID, severe heart block without a pacemaker, pregnant/breastfeeding women, certain neuromuscular diseases, prisoners, magnesium allergy or high serum magnesium levels.

Inclusion Criteria

I am an adult with mesothelioma planning surgery with HIOC at BWH.

Exclusion Criteria

Conflict with other study

I am not in a study that could affect my IV magnesium treatment.

I have had significant heart artery blockage or surgery for it in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive either high-dose IV magnesium or placebo during surgery with HIOC

1 day

Intraoperative administration

Immediate Postoperative Monitoring

Participants are monitored for serum magnesium levels and other secondary outcomes

2 days

Continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of AKI and other outcomes

7 days

Daily monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Magnesium Sulfate

Trial Overview The study is testing if giving high-dose IV Magnesium can reduce the risk of AKI in patients getting intraoperative chemotherapy with cisplatin for mesothelioma compared to a placebo (Normal Saline).

How Is the Trial Designed?

Group I: Magnesium Sulfate Experimental Treatment 1 Intervention

The IV Mg will start at 1 g/hour (25 ml/hour) within one hour following induction of anesthesia and stabilization of the patient. The infusion will continue for 24 hours and serum Mg levels will be monitored every 4 hours (+/-1 hour) for 28 hours following initiation of the Mg. Dose adjustments to the Mg infusion will be made as necessary to reach target serum Mg levels (3-5 mg/dl).

Group II: Normal Saline Placebo Group 1 Intervention

Patients randomized to placebo will receive an equal volume of normal saline (0.9% NS) placebo which will be administered as a continuous infusion at 25 ml/hour. The infusion will continue for 24 hours.

Magnesium Sulfate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Magnesium sulfate for:

• Seizure prevention in pre-eclampsia
• Asthma exacerbation treatment
• Constipation treatment

Approved in European Union as Magnesium sulphate for:

• Pre-eclampsia and eclampsia treatment
• Hypomagnesemia treatment

Approved in Canada as Magnesium sulfate for:

• Seizure prevention in pre-eclampsia
• Asthma exacerbation treatment

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

Magnesium sulfate (MgSO4) was highly effective in controlling seizures in 459 cases of eclampsia, with a very low recurrence rate of only 1.31%.

The treatment demonstrated a low incidence of toxicity, with no life-threatening side effects, and resulted in a maternal mortality rate of 3.70% and perinatal mortality of 9.15%, indicating a good prognosis for both mothers and their babies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of magnesium sulphate (MgSO4) in the treatment of eclampsia. Alauddin, M., Sarkar, MK., Munshi, S., et al.[2012]

In a study of 39 obstetrical patients with eclampsia over 7 years, magnesium sulfate (MgSO4) was used in 92% of cases for secondary prevention, highlighting its effectiveness in managing this serious condition.

The study reported low maternal (2.5%) and perinatal (11%) mortality rates, suggesting that MgSO4 is a safe and effective treatment for eclampsia when used according to established guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Magnesium sulfate in the prophylaxis of eclampsia: a retrospective study]. Bourret, B., Compère, V., Torre, S., et al.[2012]

Magnesium sulfate is widely used in obstetrics for preventing seizures in women with preeclampsia and for stopping preterm labor, but it carries a risk of accidental overdose that can harm both mothers and babies.

Despite its routine use, vigilance is essential to ensure safety, and following the recommendations in this article can help reduce the risk of overdose and improve error detection before serious harm occurs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obstetrical accidents involving intravenous magnesium sulfate: recommendations to promote patient safety. Simpson, KR., Knox, GE.[2019]

Sulfated polysaccharides from various seaweeds showed significant antiviral activity against dengue virus, particularly DENV-2, with effective concentrations ranging from 0.12 to 20 μg/mL.

The antiviral effectiveness of these polysaccharides is influenced by their sulfate content, the positioning of sulfate groups, sugar composition, and molar mass, primarily acting during the virus's adsorption and internalization phases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiviral activity against dengue virus of diverse classes of algal sulfated polysaccharides. Pujol, CA., Ray, S., Ray, B., et al.[2023]

A study of 90 magnesium sulphate injection samples in Anambra state found that 20% from Onitsha lacked proper registration, indicating potential issues with drug quality.

While all samples passed microbiological tests, 20% from Onitsha and 33.3% from Nnewi failed pH analysis, highlighting the presence of substandard products that could affect treatment outcomes for preeclampsia and eclampsia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emergency medicine: magnesium sulphate injections and their pharmaceutical quality concerns. Oli, AN., Nwankwo, EJ., Umeyor, CE., et al.[2022]

An aqueous extract from the brown marine alga Sargassum kjellmanianum showed effectiveness in inhibiting the growth of Sarcoma-180 cells but was initially ineffective against L-1210 leukemia cells.

After sulfating a polysaccharide fraction from the alga, the resulting compound demonstrated a 26% increase in effectiveness against L-1210 leukemia, suggesting that the sulfation process enhances its antitumor properties, potentially through immune response activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor effect of seaweeds. IV. Enhancement of antitumor activity by sulfation of a crude fucoidan fraction from Sargassum kjellmanianum. Yamamoto, I., Takahashi, M., Suzuki, T., et al.[2003]

Marine sulfated polysaccharides (MSPs) have shown promising antiviral effects against SARS-CoV-2, with nine candidates identified as potential inhibitors, including five that had not been previously reported for this purpose.

Molecular docking studies suggest that MSPs can bind to the receptor-binding domain of the SARS-CoV-2 spike protein and human ACE2, potentially blocking the virus from entering human cells, similar to the action of heparin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Marine Sulfated Polysaccharides as Promising Antiviral Agents: A Comprehensive Report and Modeling Study Focusing on SARS CoV-2. Salih, AEM., Thissera, B., Yaseen, M., et al.[2021]

Polyanions, which are negatively charged macromolecules, have shown potential as antiviral agents against enveloped viruses like SARS-CoV-2 by forming complexes with viral proteins, but their effectiveness in vivo has been limited due to interactions with blood components.

The study suggests using polysulfates to inhibit coronaviruses in the airways through methods like sprays or nebulization, highlighting the need for biocompatibility and biofunctionality tests to ensure safety and effectiveness in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The non-specific antiviral activity of polysulfates to fight SARS-CoV-2, its mutants and viruses with cationic spikes. Vert, M.[2022]

Magnesium sulfate (MgSO4) treatment in obstetrics has been associated with negative effects on the fetus and newborn, raising concerns about its safety in these populations.

There are conflicting reports regarding the tocolytic efficacy of magnesium sulfate, meaning its effectiveness in stopping preterm labor is still debated among researchers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficiency and safety of magnesium sulfate treatment in obstetrics]. Mikołajek, W., Chlubek, D.[2017]

The sulfated exopolysaccharide p-KG03 from the marine microalga Gyrodinium impudicum shows significant antiviral activity against the encephalomyocarditis virus (EMCV) with an effective concentration (EC50) of 26.9 microg/ml, effectively inhibiting cytopathic effects in infected cells.

Importantly, p-KG03 demonstrated no cytotoxic effects on HeLa cells at concentrations up to 1000 microg/ml, indicating its potential safety for further development as an antiviral agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiviral effects of sulfated exopolysaccharide from the marine microalga Gyrodinium impudicum strain KG03. Yim, JH., Kim, SJ., Ahn, SH., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10592264/

High-Dose IV Magnesium in Mesothelioma Patients ... Although not proven by a randomized clinical trial (RCT), HIOC is associated with improved survival outcomes in patients with mesothelioma who ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0048969725003006

The cytotoxic/genotoxic role of impurities in soluble minerals This toxicological evaluation may become even more effective compared to a synthetic magnesium sulphate (Epsom salt), which does not contain ...

3. researchgate.net researchgate.net/publication/373910228_High-dose_IV_magnesium_in_mesothelioma_patients_receiving_surgery_with_hyperthermic_intraoperative_cisplatin_Pilot_studies_and_design_of_a_phase_II_randomized_clinical_trial

Pilot studies and design of a phase II randomized clinical trial The rate of the primary outcome was not significantly different in the magnesium sulfate group and the placebo group (11.3% and 11.7%, respectively ...

4. oaepublish.com oaepublish.com/articles/2394-4722.2019.008

Electrolyte disorders in cancer patients: a systematic review Electrolyte disorders are very common complications in cancer patients. They might be associated to a worsening outcome, influencing quality of life.

5. go.drugbank.com go.drugbank.com/drugs/DB00653

Magnesium sulfate: Uses, Interactions, Mechanism of Action Magnesium sulfate can cause a decrease in the absorption of Alendronic acid resulting in a reduced serum concentration and potentially a decrease in efficacy.

6. cir-safety.org cir-safety.org/sites/default/files/magnes062014final.pdf

Safety Assessment of Magnesium Sulfate as Used in ... Magnesium sulfate is an FDA-approved direct food additive that is generally recognized as safe.11 Additionally,. FDA has stated that magnesium ...

7. journals.sagepub.com journals.sagepub.com/doi/10.1177/1091581818773355

Safety Assessment of Magnesium Sulfate as Used in ... The Panel concluded that magnesium sulfate is safe in cosmetics in the present practices of use and concentration described in the safety assessment.