Low-dose ketamine infusion for the treatment of multiple sclerosis fatigue (INKLING-MS): Study protocol for a randomized, double-blind, active placebo-controlled phase II trial

Abstract

BackgroundFatigue is one of the most common symptoms of people with Multiple Sclerosis (MS). However, currently-used medications for the treatment of fatigue probably do not work better than a placebo. In a pilot trial, we showed that one infusion of low-dose ketamine significantly improved fatigue severity measured four weeks after the infusion. MethodsThe proposed study is a single-center, phase II, randomized, double-blind, parallel-group, active-placebo-controlled trial of intravenous low-dose ketamine in patients with MS fatigue. Participants will be randomized 1:1:1 into three groups: receiving either one or two infusions of ketamine (0.5 mg/kg over 40 min) or zero to one infusion of the active placebo (midazolam, 0.05 mg/kg over 40 min).Eligibility criteria include adult patients diagnosed with MS based on the latest criteria, complaining of fatigue as one of the main symptoms, and having a screening MFIS score higher than a pre-specified threshold. ResultsOne hundred and ten participants will be randomized over 30 months at Johns Hopkins MS Center. Complete enrollment is expected by mid-2025. The study's primary outcome will be the MFIS score at the end of week 4, comparing two-thirds of the participants who received ketamine with one-third who received midazolam. The secondary and exploratory outcomes (measured four weeks after the second infusion) will show how long the effects of a single infusion last and if two infusions of ketamine are better than one in improving MS fatigue. ConclusionThis study can show whether intervening in the glutamatergic pathways would improves MS fatigue.