Contributions
Abstract: P902
Type: Poster Sessions
Abstract Category: Therapy - Neuroprotection and Repair
Introduction: Prolactin enhances remyelination in animal models but clinical trials are stymied by the absence of marketed prolactin. Domperidone however, is a safe, inexpensive drug which raises serum prolactin levels. It may be an alternative to administration of prolactin.
Objectives and Aims: In an ongoing phase 2 randomized, controlled trial we are comparing domperidone to no treatment as add-on therapy in patients with relapsing remitting multiple sclerosis (RRMS) taking an approved disease modifying therapy (DMT) (NCT02493049). Goals of the trial include confirmation that domperidone raises serum prolactin levels in RRMS patients, and characterization of the magnitude and variability of prolactin levels.
Methods: Consenting DMT treated RRMS patients, age 18-60 years, with contrast enhancing lesions on a monitoring MRI, were randomized to domperidone (10 mg three times daily) or no treatment. Serum prolactin was measured at screen, week 6 and week 16.
Results: Between October 2015 and April 2018, 695 patients were contacted by telephone; 239/695 (34%) consented to participate. To date, screening MRI scans have been completed in 199 participants. Contrast enhancing lesions were detected in 18 (9%) participants; 15 (8%) were randomized.
The mean screening prolactin level was 11.5 (SD 5.2) µg/L and did not differ between participants with and without enhancing lesions or between those randomized to prolactin and no treatment. Normal levels are ≤15 µg/L for men and ≤25 µg/L for women. At week 6, the serum prolactin level was higher in all domperidone-treated participants (mean 106.0, SD 64.5, n=9) than controls (mean 15.2, SD 6.3, n=5) (t-test P=0.009). It remained higher at week 16 (92.3, SD 61.0, n=7) compared with controls (12.3, SD 4.8, n=4) (t-test P=0.03).
Conclusions: Domperidone consistently increased prolactin levels in participants with RRMS. An 8-fold increase was observed by week 6 and was maintained at week 16. Domperidone therefore, appears to be a reasonable substitute for prolactin administration in patients with RRMS.
Disclosure: Wei-Qiao Liu: received travel grants from EMD Serono to participate at conferences and educational events; participated in advisory boards for EMD Serono and Novartis.
Jamie Greenfield: nothing to disclose.
Rand Pasha: nothing to disclose.
Graziela Cerchiaro: nothing to disclose.
Yunyan Zhang: Nothing to disclose.
V. Wee Yong: nothing to disclose.
G. Bruce Pike: nothing to disclose.
Luanne M. Metz: nothing to disclose.
Abstract: P902
Type: Poster Sessions
Abstract Category: Therapy - Neuroprotection and Repair
Introduction: Prolactin enhances remyelination in animal models but clinical trials are stymied by the absence of marketed prolactin. Domperidone however, is a safe, inexpensive drug which raises serum prolactin levels. It may be an alternative to administration of prolactin.
Objectives and Aims: In an ongoing phase 2 randomized, controlled trial we are comparing domperidone to no treatment as add-on therapy in patients with relapsing remitting multiple sclerosis (RRMS) taking an approved disease modifying therapy (DMT) (NCT02493049). Goals of the trial include confirmation that domperidone raises serum prolactin levels in RRMS patients, and characterization of the magnitude and variability of prolactin levels.
Methods: Consenting DMT treated RRMS patients, age 18-60 years, with contrast enhancing lesions on a monitoring MRI, were randomized to domperidone (10 mg three times daily) or no treatment. Serum prolactin was measured at screen, week 6 and week 16.
Results: Between October 2015 and April 2018, 695 patients were contacted by telephone; 239/695 (34%) consented to participate. To date, screening MRI scans have been completed in 199 participants. Contrast enhancing lesions were detected in 18 (9%) participants; 15 (8%) were randomized.
The mean screening prolactin level was 11.5 (SD 5.2) µg/L and did not differ between participants with and without enhancing lesions or between those randomized to prolactin and no treatment. Normal levels are ≤15 µg/L for men and ≤25 µg/L for women. At week 6, the serum prolactin level was higher in all domperidone-treated participants (mean 106.0, SD 64.5, n=9) than controls (mean 15.2, SD 6.3, n=5) (t-test P=0.009). It remained higher at week 16 (92.3, SD 61.0, n=7) compared with controls (12.3, SD 4.8, n=4) (t-test P=0.03).
Conclusions: Domperidone consistently increased prolactin levels in participants with RRMS. An 8-fold increase was observed by week 6 and was maintained at week 16. Domperidone therefore, appears to be a reasonable substitute for prolactin administration in patients with RRMS.
Disclosure: Wei-Qiao Liu: received travel grants from EMD Serono to participate at conferences and educational events; participated in advisory boards for EMD Serono and Novartis.
Jamie Greenfield: nothing to disclose.
Rand Pasha: nothing to disclose.
Graziela Cerchiaro: nothing to disclose.
Yunyan Zhang: Nothing to disclose.
V. Wee Yong: nothing to disclose.
G. Bruce Pike: nothing to disclose.
Luanne M. Metz: nothing to disclose.