Contributions
Abstract: P1208
Type: Poster
Abstract Category: Therapy - disease modifying - Neurorepair
Objectives: We are conducting a phase 2, single-centre, randomized, controlled trial comparing domperidone add-on therapy versus no add-on therapy in relapsing remitting multiple sclerosis (RRMS) patients taking disease modifying therapy (DMT) and who have breakthrough lesions identified on MRI monitoring. Our primary objectives are:
(1) to demonstrate that we can recruit to this trial; and
(2) to obtain estimates of the magnitude and variability of lesion repair over 32 weeks.
Background: Prolactin enhances remyelination in animal models but moving to clinical trials is challenged by the lack of a marketed prolactin and lack of a clinical model to evaluate lesion repair, other than possibly optic neuritis. While prolactin can be produced we have chosen to use domperidone, a safe, inexpensive drug marketed to enhance gastric motility because it also raises serum prolactin levels sufficiently to be used off-label to improve lactation.
Methods: Consenting RRMS patients aged 18-60, taking an approved DMT, and shown to have breakthrough gadolinium enhancing lesions on DMT monitoring MRI, will be randomized (2:1) to domperidone add-on treatment 10 mg three times daily or no add-on treatment. After screening and baseline visits, follow-up will be at 6, 16, and 32 weeks. MRI scans will be obtained at baseline, 16 and 32 weeks. In addition to routine MRI sequences, we will evaluate and compare three MRI measures [texture analysis, diffusion tensor imaging (DTI), and magnetization transfer imaging (MTI)] for their ability to measure repair within acute enhancing lesions. We aim to enroll 24 patients over 36 months.
Results: Recruitment is ongoing. Between November 2015 and April 2016 we screened 25 patients; 12 more are scheduled for screening. One patient has been randomized to domperidone and has tolerated treatment without any adverse effects. As expected, the majority of screen failures are due to the absence of enhancing lesions on MRI.
Conclusions: We intend to determine if this trial model is appropriate for studying lesion repair in MS and determine if any of these imaging methods are sensitive enough to measure repair within enhancing lesions. We will present the study design and updated recruitment data. Recruitment was slow in the first few months but many more patients are currently being scheduled for screening. We anticipate that the results from this trial will inform the design of future phase 2 trials of therapies to promote lesion repair in MS.
Disclosure:
Liu, W.-Q.: nothing to disclose.
Zhornitsky, S.: nothing to disclose.
Greenfield, J.: nothing to disclose.
Pasha, R.: nothing to disclose.
Cerchiaro Farah, G.: nothing to disclose.
Zhang, Y.: nothing to disclose.
Pike, G.B.: nothing to disclose.
Yong, V.W.: nothing to disclose.
Metz, L.M.: nothing to disclose.
Abstract: P1208
Type: Poster
Abstract Category: Therapy - disease modifying - Neurorepair
Objectives: We are conducting a phase 2, single-centre, randomized, controlled trial comparing domperidone add-on therapy versus no add-on therapy in relapsing remitting multiple sclerosis (RRMS) patients taking disease modifying therapy (DMT) and who have breakthrough lesions identified on MRI monitoring. Our primary objectives are:
(1) to demonstrate that we can recruit to this trial; and
(2) to obtain estimates of the magnitude and variability of lesion repair over 32 weeks.
Background: Prolactin enhances remyelination in animal models but moving to clinical trials is challenged by the lack of a marketed prolactin and lack of a clinical model to evaluate lesion repair, other than possibly optic neuritis. While prolactin can be produced we have chosen to use domperidone, a safe, inexpensive drug marketed to enhance gastric motility because it also raises serum prolactin levels sufficiently to be used off-label to improve lactation.
Methods: Consenting RRMS patients aged 18-60, taking an approved DMT, and shown to have breakthrough gadolinium enhancing lesions on DMT monitoring MRI, will be randomized (2:1) to domperidone add-on treatment 10 mg three times daily or no add-on treatment. After screening and baseline visits, follow-up will be at 6, 16, and 32 weeks. MRI scans will be obtained at baseline, 16 and 32 weeks. In addition to routine MRI sequences, we will evaluate and compare three MRI measures [texture analysis, diffusion tensor imaging (DTI), and magnetization transfer imaging (MTI)] for their ability to measure repair within acute enhancing lesions. We aim to enroll 24 patients over 36 months.
Results: Recruitment is ongoing. Between November 2015 and April 2016 we screened 25 patients; 12 more are scheduled for screening. One patient has been randomized to domperidone and has tolerated treatment without any adverse effects. As expected, the majority of screen failures are due to the absence of enhancing lesions on MRI.
Conclusions: We intend to determine if this trial model is appropriate for studying lesion repair in MS and determine if any of these imaging methods are sensitive enough to measure repair within enhancing lesions. We will present the study design and updated recruitment data. Recruitment was slow in the first few months but many more patients are currently being scheduled for screening. We anticipate that the results from this trial will inform the design of future phase 2 trials of therapies to promote lesion repair in MS.
Disclosure:
Liu, W.-Q.: nothing to disclose.
Zhornitsky, S.: nothing to disclose.
Greenfield, J.: nothing to disclose.
Pasha, R.: nothing to disclose.
Cerchiaro Farah, G.: nothing to disclose.
Zhang, Y.: nothing to disclose.
Pike, G.B.: nothing to disclose.
Yong, V.W.: nothing to disclose.
Metz, L.M.: nothing to disclose.