PT  - JOURNAL ARTICLE
AU  - Marcus W. Koch
AU  - Kayla Sage
AU  - Sharanjit Kaur
AU  - Janet Kim
AU  - Graziela Cerchiaro
AU  - V. Wee Yong
AU  - Gary R. Cutter
AU  - Luanne M. Metz
TI  - Repurposing Domperidone in Secondary Progressive Multiple Sclerosis
AID  - 10.1212/WNL.0000000000011863
DP  - 2021 May 04
TA  - Neurology
PG  - e2313--e2322
VI  - 96
IP  - 18
4099  - http://n.neurology.org/content/96/18/e2313.short
4100  - http://n.neurology.org/content/96/18/e2313.full
SO  - Neurology2021 May 04; 96
AB  - Objective To assess whether treatment with the generic drug domperidone can reduce the progression of disability in secondary progressive multiple sclerosis (SPMS), we conducted a phase 2 futility trial following the Simon 2-stage design.Methods We enrolled patients in an open-label, Simon 2-stage, single-center, phase 2, single-arm futility trial at the Calgary Multiple Sclerosis Clinic if they met the following criteria: age of 18 to 60 years, SPMS, screening Expanded Disability Status Scale score of 4.0 to 6.5, and screening timed 25-ft walk (T25FW) of ≥9 seconds. Patients received domperidone 10 mg 4 times daily for 1 year. The primary outcome was worsening of disability, defined as worsening of the T25FW performance by ≥20% at 12 months compared to baseline. This trial is registered with ClinicalTrials.gov (NCT02308137).Results Between February 13, 2015, and January 3, 2020, 110 patients were screened, 81 received treatment, and 64 completed follow-up, of whom 62 were analyzed. The study did not meet its primary endpoint: 22 of 62 (35%) patients experienced significant worsening of disability, which is close to the expected proportion of 40% and above the predefined futility threshold. Patients with higher prolactin levels during the study had a significantly lower risk of disability progression, which may warrant further investigation. Domperidone treatment was reasonably well tolerated, but adverse events occurred in 84% and serious adverse events in 15% of patients.Conclusions Domperidone treatment could not reject futility in reducing disability progression in SPMS. The Simon 2-stage trial model may be a useful model for phase 2 studies in progressive MS.Trial Registration Information ClinicalTrials.gov Identifier: NCT02308137.Classification of Evidence This study provides Class III evidence that in individuals with SPMS participating in a futility trial, domperidone treatment could not reject futility in reducing disability progression at 12 months.ASCEND=A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis; CHREB=Conjoint Health Research Ethics Board; EDSS=Expanded Disability Status Scale; MFIS=Modified Fatigue Impact Scale; MS=multiple sclerosis; MSQOL-54=MS Related Quality of Life Scale 54-item version; 9HPT=9-hole peg test; QTc=frequency-corrected QT interval; RCT=randomized controlled trial; RRMS=relapsing-remitting MS; SDMT=Symbol Digit Modalities Test; SPMS=secondary progressive multiple sclerosis; T25FW=timed 25-ft walk