Targeting phosphocreatine metabolism in relapsing–remitting multiple sclerosis: evaluation with brain MRI, 1 H and 31 P MRS, and clinical and cognitive testing

Background/objectives Fluoxetine and prucalopride might change phosphocreatine (PCr) levels via the cAMP–PKA pathway, an interesting target in the neurodegenerative mechanisms of MS. Methods We conducted a two-center double-blind, placebo-controlled, randomized trial including 48 relapsing–remitting MS patients. Patients were randomized to receive placebo ( n = 13), fluoxetine ( n = 15), or prucalopride ( n = 14) for 6 weeks. Proton ( 1 H) and phosphorus ( 31 P) magnetic resonance spectroscopy (MRS) as well as volumetric and perfusion MR imaging were performed at weeks 0, 2, and 6. Clinical and cognitive testing were evaluated at weeks 0 and 6. Results No significant changes were observed for both 31 P and 1 H MRS indices. We found a significant effect on white matter volume and a trend towards an increase in grey matter and whole brain volume in the fluoxetine group at week 2; however, these effects were not sustained at week 6 for white matter and whole brain volume. Fluoxetine and prucalopride showed a positive effect on 9-HPT, depression, and fatigue scores. Conclusion Both fluoxetine and prucalopride had a symptomatic effect on upper limb function, fatigue, and depression, but this should be interpreted with caution. No effect of treatment was found on 31 P and 1 H MRS parameters, suggesting that these molecules do not influence the PCr metabolism.