Magnesium Sulfate for Mesothelioma
(MAGIC-AKI Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Brigham and Women's Hospital
Disqualifiers: Kidney disease, Neuromuscular disease, Coronary artery disease, others
Prior Safety Data
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?In this research study, investigators will test whether prophylactic high-dose IV Mg administration attenuates the risk of AKI in patients with malignant mesothelioma receiving intraoperative chemotherapy (HIOC) with cisplatin compared to placebo
.
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 magnesium sulfate safe for use in humans?
Magnesium sulfate is generally considered safe for use in humans, especially in obstetrics for conditions like eclampsia, with a low incidence of toxicity. However, there is a risk of accidental overdose, which can be harmful, so careful monitoring is necessary.
12345How does the drug Magnesium Sulfate differ from other treatments for mesothelioma?
Magnesium Sulfate is unique for mesothelioma treatment as it is not a standard therapy for this condition, and its use is being explored for its potential benefits, unlike traditional chemotherapy or radiation treatments.
678910Eligibility Criteria
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.
+10 more
Trial Timeline
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
Participant Groups
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).
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Magnesium SulfateExperimental Treatment1 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 SalinePlacebo Group1 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, Australia 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
🇦🇺 Approved in Australia as Magnesium sulphate for:
- Pre-eclampsia and eclampsia treatment
- Hypomagnesemia treatment
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Brigham and Women's HospitalBoston, MA
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Who Is Running the Clinical Trial?
Brigham and Women's HospitalLead Sponsor
National Institutes of Health (NIH)Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Collaborator
References
[Efficiency and safety of magnesium sulfate treatment in obstetrics]. [2017]Current views on efficacy and safety of magnesium sulfate treatment in obstetrics are presented. Negative effects of MgSO4 on fetus and newborn are described. Contradictory reports dealing with tocolytic efficacy of magnesium sulfate are discussed.
Obstetrical accidents involving intravenous magnesium sulfate: recommendations to promote patient safety. [2019]Magnesium sulfate is commonly used in obstetrical practice both as seizure prophylaxis in women with preeclampsia, as well as to inhibit preterm labor contractions. However, despite (and perhaps because of) years of use and provider familiarity, the administration of magnesium sulfate occasionally results in accidental overdose and patient harm. Fortunately, in most instances when potentially fatal amounts of magnesium sulfate are given, the error is recognized before permanent adverse outcomes occur. Nevertheless, a significant and sometimes unappreciated risk of harm to mothers and babies continues to exist. Intravenous magnesium sulfate treatment has become routine practice in obstetrics, but this does not lessen the vigilance required for safe care for mothers and babies. Implementation of the recommendations provided in this article will promote patient safety and decrease the likelihood of an accidental overdose, as well as increase the chances of identifying an error before a significant adverse outcome occurs.
Efficacy and safety of magnesium sulphate (MgSO4) in the treatment of eclampsia. [2012]Use of magnesium sulphate (MgSO4) in the treatment of eclampsia has not yet become universal probably due to some perceived apprehension about its efficacy and toxicity. This study aimed to assess, in addition to foetomaternal outcome, its efficacy to control fits in eclampsia and toxicity if any. Fit control, occurence of toxicity and foetomaternal outcome were noted in 459 cases of eclampsia treated with MgSO4. MgSO4 was very effective in controlling fits with a very low (1.31%) fit recurrence rate and had an even lower incidence of toxicity (as evidenced by sluggish patellar reflex). None of the cases developed any life threatening toxicity like respiratory paralysis. Maternal mortality rate was 3.70% and perinatal mortality 9.15%. The results suggest that MgSO4 is very safe and effective for treating eclampsia and offers good prognosis for both mother and foetus.
[Magnesium sulfate in the prophylaxis of eclampsia: a retrospective study]. [2012]The use of magnesium sulfate (MgSO(4)) has been advocated since 2000 in France in the management of eclampsia. The aim of this study was to determine the frequency of use of this treatment for eclampsia in a French department.
Emergency medicine: magnesium sulphate injections and their pharmaceutical quality concerns. [2022]World Health Organization has recognized magnesium sulphate as the drug of choice for prevention and treatment of fits associated with preeclampsia and eclampsia which are amongst the leading causes of maternal morbidity and mortality. In this study, the pharmaceutical quality of magnesium sulphate injections marketed in Anambra state was assessed.
Antitumor effect of seaweeds. IV. Enhancement of antitumor activity by sulfation of a crude fucoidan fraction from Sargassum kjellmanianum. [2003]We have reported an antitumor aqueous extract from a brown marine alga Sargassum kjellmanianum ("Hahakimoku" in Japanese). Although the extract was effective in the in vivo growth inhibition of the implanted Sarcoma-180 cells, it was not effective against L-1210-bearing mice. In the present study, we attempted to obtain a polysaccharide fraction with antitumor activity against L-1210 leukemia from this alga, on the assumption that the main active substance may be sulfated polysaccharide, especially fucoidan which is mainly composed of L-fucose and ester sulfate. Two kinds of polysaccharide fractions (SKCF and SKCF-F), which contained L-fucose and ester sulfate in the amount of 12.6% and 15.4%, 23.5% and 17.2% respectively, were first prepared starting with extraction with cold-hydrochloric acid, and their antitumor activity was examined. It was found however that they are not effective. Sulfation of SKCF was then carried out. The resulting sulfate (Sulfated SKCF) was observed to contain nearly 50% more ester sulfate than in SKCF and to be effective against L-1210 leukemia showing an ILS value of 26%. Mechanisms of antitumor action of this sulfate were also discussed from the viewpoints of negativity of ester sulfate and of activation of host-mediated immune response as known in antitumor polysaccharide preparations from other sources.
Antiviral activity against dengue virus of diverse classes of algal sulfated polysaccharides. [2023]Diverse classes of sulfated polysaccharides obtained from the red seaweeds (Rhodophyta) Grateloupia indica, Scinaia hatei and Gracilaria corticata, the brown seaweeds (Phaeophyta) Stoechospermum marginatum and Cystoseira indica and the green seaweed (Chlorophyta) Caulerpa racemosa were assayed for antiviral activity against the four serotypes of dengue virus (DENV). DENV-2 was the most susceptible serotype to all polysulfates, with inhibitory concentration 50% values in the range 0.12-20 μg/mL. The antiviral potency of the sulfated polysaccharides depended on the sulfate content, the position of sulfate group, the sugar composition, and the molar mass. Independently of the sugar composition, the antiviral effect was mainly exerted during DENV-2 adsorption and internalization.
Marine Sulfated Polysaccharides as Promising Antiviral Agents: A Comprehensive Report and Modeling Study Focusing on SARS CoV-2. [2021]SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is a novel coronavirus strain that emerged at the end of 2019, causing millions of deaths so far. Despite enormous efforts being made through various drug discovery campaigns, there is still a desperate need for treatments with high efficacy and selectivity. Recently, marine sulfated polysaccharides (MSPs) have earned significant attention and are widely examined against many viral infections. This article attempted to produce a comprehensive report about MSPs from different marine sources alongside their antiviral effects against various viral species covering the last 25 years of research articles. Additionally, these reported MSPs were subjected to molecular docking and dynamic simulation experiments to ascertain potential interactions with both the receptor-binding domain (RBD) of SARS CoV-2's spike protein (S-protein) and human angiotensin-converting enzyme-2 (ACE2). The possible binding sites on both S-protein's RBD and ACE2 were determined based on how they bind to heparin, which has been reported to exhibit significant antiviral activity against SARS CoV-2 through binding to RBD, preventing the virus from affecting ACE2. Moreover, our modeling results illustrate that heparin can also bind to and block ACE2, acting as a competitor and protective agent against SARS CoV-2 infection. Nine of the investigated MSPs candidates exhibited promising results, taking into consideration the newly emerged SARS CoV-2 variants, of which five were not previously reported to exert antiviral activity against SARS CoV-2, including sulfated galactofucan (1), sulfated polymannuroguluronate (SPMG) (2), sulfated mannan (3), sulfated heterorhamnan (8), and chondroitin sulfate E (CS-E) (9). These results shed light on the importance of sulfated polysaccharides as potential SARS-CoV-2 inhibitors.
The non-specific antiviral activity of polysulfates to fight SARS-CoV-2, its mutants and viruses with cationic spikes. [2022]Polyanions are negatively charged macromolecules known for several decades as inhibitors of many viruses in vitro, notably AIDS virus. In the case of enveloped viruses, this activity was assigned to the formation of a polyelectrolyte complex between an anionic species, the polyanion, and the spike cationic proteins which are, for polymer chemists, comparable to cationic polyelectrolytes. Unfortunately, in vitro antiviral activity was not confirmed in vivo, possibly because polyanions were captured by cationic blood elements before reaching target cells. Accordingly, virologists abandoned the use of polyanions for antiviral therapy. In the case of coronaviruses like SARS-CoV-2 and its mutants the game may not be over because these viruses infect cells of airways and not of blood. This communication proposes strategies to use polysulfates to attack and inhibit viral particles before they reach target cells in the airways. For this, polysulfate solutions may be administered by spray, gargling and nebulization or used to capture virus-containing droplets and aerosols by bubbling when these vectors are in the atmosphere. The technical means exist. However, biocompatibility and biofunctionality tests are necessary in the case of airways. Such tests require manipulation of pathogens, something which is beyond the competences of a biomaterialist. For this, a specialist in virology is necessary. Attempts to find one failed so far despite all-around solicitations over the past ten months and despite the fact that attacking the virus with polysulfates may complement beneficially the defensive strategies based on masks, vaccines and hospitals.
Antiviral effects of sulfated exopolysaccharide from the marine microalga Gyrodinium impudicum strain KG03. [2018]The sulfated exopolysaccharide p-KG03, which is produced by the marine microalga Gyrodinium impudicum strain KG03, exhibited impressive antiviral activity in vitro (EC50 = 26.9 micro g/ml) against the encephalomyocarditis virus (EMCV). Depending on the p-KG03 concentration, the development of cytopathic effects in EMCV-infected HeLa cells was either inhibited completely or slowed. Moreover, p-KG03 did not show any cytotoxic effects on HeLa cells, even at concentrations up to 1000 microg/ml. The polysaccharide was purified by repeated precipitation in ethanol, followed by gel filtration. The p-KG03 polysaccharide had a molecular weight of 1.87 x 10(7), and was characterized as a homopolysaccharide of galactose with uronic acid (2.96% wt/wt) and sulfate groups (10.32% wt/wt). The biological activities of p-KG03 suggest that sulfated metabolites from marine organisms are a rich source of antiviral agents. This is the first reported marine source of antiviral sulfated polysaccharides against EMCV. The p-KG03 polysaccharide may be useful in the development of marine bioactive exopolysaccharide for biotechnological and pharmaceutical products.