An open label, single arm, phase II futility trial of Domperidone treatment in secondary progressive MS. Results of the first stage of the trial
ECTRIMS Online Library. Koch M. 10/25/17; 199799; EP1779
Marcus Koch
Marcus Koch
Contributions
Abstract

Abstract: EP1779

Type: ePoster

Abstract Category: Therapy - disease modifying - 31 Treatment of progressive MS

Background: Secondary progressive Multiple Sclerosis (SPMS) is characterized by slow and relentless worsening of disability independent of relapses. In SPMS multiple pathological processes are contributing to the accumulation of disability. The protein hormone prolactin has been shown in animal studies to have neuroprotective properties and to improve remyelination. We hypothesize that increasing systemic prolactin levels in patients with SPMS may slow disability progression. Domperidone is a generic dopamine D2 receptor antagonist that increases prolactin levels in humans. In this clinical trial, we used the Simon-2-Stage Futility Trial model to investigate the effect of Domperidone treatment on disease progression in patients with SPMS.
Methods and design: This trial is a one year phase II Simon-2-Stage Futility Trial. The primary endpoint was clinical worsening defined as worsening by 20% or more on the timed 25 foot walk between baseline and one year follow-up. Based on natural history and original trial data, we expected 40% of the trial cohort to have clinical worsening. The futility threshold was set at 25% of worsening in the trial cohort, using a type 1 error rate of 5% and 80% power. Domperidone treatment is deemed futile if 12 or more of 30 patients enrolled in stage 1 of the trial have clinical worsening at one year follow-up. In the first stage of the trial, 30 patients with SPMS were treated with 40mg of Domperidone daily for 12 months. Trial Registration: Clinicatrials.gov NCT02308137
Results: Overall 52 patients were screened of whom 35 were enrolled. Five patients terminated the trial early. The median age at baseline of the 30 patients who finished the trial was 54 years, 23 (77%) were female, none of the trial participants were using disease modifying treatments. Median serum prolactin levels (normal range: 0-25 mg/L) increased from 9 (interquartile range: 7-12) mg/L at screening to 92 (interquartile range: 38-140.5) mg/L at one month follow-up. At one year follow-up 8 patients had clinical worsening, significantly less than the historical rate of 40% (p< 0.05).
Discussion: After the first stage of this two stage trial, fewer patients than expected experienced clinical worsening. Domperidone treatment increased serum prolactin levels in the trial cohort. Domperidone treatment is deemed non-futile at this interim stage of the trial. The trial continues into the second stage.
Disclosure: This study was funded by Alberta Innovates Health Solutions (AIHS) through the Collaborative Research and Innovations (CRIO) Team Grant 'Medicines for Remyelination in Multiple Sclerosis (MS): The Next Frontier' .
Marcus Koch: nothing to disclose
Janet Kim: nothing to disclose
Graziela Cerchiaro: nothing to disclose
Wee Yong: nothing to disclose
Gary Cutter: nothing to disclose
Luanne Metz: nothing to disclose

Abstract: EP1779

Type: ePoster

Abstract Category: Therapy - disease modifying - 31 Treatment of progressive MS

Background: Secondary progressive Multiple Sclerosis (SPMS) is characterized by slow and relentless worsening of disability independent of relapses. In SPMS multiple pathological processes are contributing to the accumulation of disability. The protein hormone prolactin has been shown in animal studies to have neuroprotective properties and to improve remyelination. We hypothesize that increasing systemic prolactin levels in patients with SPMS may slow disability progression. Domperidone is a generic dopamine D2 receptor antagonist that increases prolactin levels in humans. In this clinical trial, we used the Simon-2-Stage Futility Trial model to investigate the effect of Domperidone treatment on disease progression in patients with SPMS.
Methods and design: This trial is a one year phase II Simon-2-Stage Futility Trial. The primary endpoint was clinical worsening defined as worsening by 20% or more on the timed 25 foot walk between baseline and one year follow-up. Based on natural history and original trial data, we expected 40% of the trial cohort to have clinical worsening. The futility threshold was set at 25% of worsening in the trial cohort, using a type 1 error rate of 5% and 80% power. Domperidone treatment is deemed futile if 12 or more of 30 patients enrolled in stage 1 of the trial have clinical worsening at one year follow-up. In the first stage of the trial, 30 patients with SPMS were treated with 40mg of Domperidone daily for 12 months. Trial Registration: Clinicatrials.gov NCT02308137
Results: Overall 52 patients were screened of whom 35 were enrolled. Five patients terminated the trial early. The median age at baseline of the 30 patients who finished the trial was 54 years, 23 (77%) were female, none of the trial participants were using disease modifying treatments. Median serum prolactin levels (normal range: 0-25 mg/L) increased from 9 (interquartile range: 7-12) mg/L at screening to 92 (interquartile range: 38-140.5) mg/L at one month follow-up. At one year follow-up 8 patients had clinical worsening, significantly less than the historical rate of 40% (p< 0.05).
Discussion: After the first stage of this two stage trial, fewer patients than expected experienced clinical worsening. Domperidone treatment increased serum prolactin levels in the trial cohort. Domperidone treatment is deemed non-futile at this interim stage of the trial. The trial continues into the second stage.
Disclosure: This study was funded by Alberta Innovates Health Solutions (AIHS) through the Collaborative Research and Innovations (CRIO) Team Grant 'Medicines for Remyelination in Multiple Sclerosis (MS): The Next Frontier' .
Marcus Koch: nothing to disclose
Janet Kim: nothing to disclose
Graziela Cerchiaro: nothing to disclose
Wee Yong: nothing to disclose
Gary Cutter: nothing to disclose
Luanne Metz: nothing to disclose

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