The Safety and Efficacy of Oral Magnesium Pidolate in Children with Hemoglobin SC Disease.

An important characteristic of the Hb SC erythrocyte is its high intracellular Hb concentration, which is due to cell K⁺ loss and dehydration mediated by an abnormally active K-Cl co-transport. This pathologic state of cellular dehydration raises the intracellular concentration of Hb S, thereby increasing its tendency to polymerize. Previous studies in patients with sickle cell disease have shown that oral Mg supplements can increase erythrocyte Mg content, reduce the activity of K-Cl co-transport and diminish erythrocyte dehydration. We performed a randomized, double blind, placebo-controlled study with crossover design on oral Mg supplementation in children with HbSC disease.

Methods: Two major pediatric sickle cell centers participated in this IRB-approved study: Texas Children’s Sickle Cell Center and The Children’s Hospital in Boston. Over 100 eligible patients were contacted and invited to participate. The enrolled patients or their parents/guardians gave informed consent. Patients were randomized to either receive oral Mg pidolate or placebo for 6 months followed by a wash-out period of 2 months, then followed by a 6 month period of the other agent (placebo/Mg pidolate) and 2 months wash-out. Patients were initially followed every 2 weeks, then every 4 weeks. Safety was assessed both by clinical assessment as well as laboratory evaluation, including serum magnesium levels.

Results: Between January 2002 and December 2004 we enrolled 12 patients (7 males, 5 female, age range 3.9 to 16.8 years) with HbSC disease and at least one pain crisis within the last year. Only 5 patients are fully evaluable for efficacy assessment. Seven patients came off study for the following reasons: 3 for non-compliance, 2 for study violation (pharmacy dispensed wrong formulation), and 2 withdrew for personal reasons (no longer interested), but all of them were included in the safety assessment. There were 3 events that were considered probably related to study drug (or placebo): diarrhea, grade 2 once and headaches, grade 3, in 2 instances. There were 6 events possibly related to drug (or placebo): diarrhea in three patients (all grade 1) and headaches of grade 2 or 3 in three patients. All adverse events resolved without stopping the drug/placebo. The results of the intracellular Mg concentrations and thus efficacy analysis will be available after unblinding the study in September 2005.

Conclusion: Mg pidolate appears to be safe and well-tolerated when used in children with HbSC disease. No serious adverse events occurred that were considered definitively related to the study drug(s). Efficacy results will be available at the time of the meeting. However, despite the fact that study was open at 2 major sickle cell centers and had relatively non-restrictive enrollment criteria, accrual was extremely slow, presumably due to the sporadic and rather low disease intensity of Hb SC disease, and several patients did not complete the study. This should be taken into consideration when designing larger studies for patients with HbSC disease exclusively.