Randomized, Placebo-Controlled, Double-Blind Pilot Study of D-Cycloserine in Chronic Stroke

Andrew J Butler, Justiss Kallos, Stephen N Housley, Michelle C LaPlaca, Stephen F Traynelis, Steven L Wolf, Andrew J Butler, Justiss Kallos, Stephen N Housley, Michelle C LaPlaca, Stephen F Traynelis, Steven L Wolf

Abstract

Stroke is a leading cause of death and disability in the USA. Up to 60% of patients do not fully recover despite intensive physical therapy treatment. N-Methyl-D-aspartate receptors (NMDA-R) have been shown to play a role in synaptic plasticity when activated. D-Cycloserine promotes NMDA receptor function by binding to receptors with unoccupied glycine sites. These receptors are involved in learning and memory. We hypothesized that D-cycloserine, when combined with robotic-assisted physiotherapy (RAP), would result in greater gains compared with placebo + RAP in stroke survivors. Participants (n = 14) were randomized to D-cycloserine plus RAP or placebo plus RAP. Functional, cognitive, and quality-of-life measures were used to assess recovery. There was significant improvement in grip strength of the affected hand within both groups from baseline to 3 weeks (95% confidence interval for mean change, 3.95 ± 2.96 to 4.90 ± 3.56 N for D-cycloserine and 5.72 ± 3.98 to 8.44 ± 4.90 N for control). SIS mood domain showed improvement for both groups (95% confidence interval for mean change, 72.6 ± 16.3 to 82.9 ± 10.9 for D-cycloserine and 82.9 ± 13.5 to 90.3 ± 9.9 for control). This preliminary study does not provide evidence that D-cycloserine can provide greater gains in learning compared with placebo for stroke survivors.

Figures

Figure 1
Figure 1
Experimental design and time course of the study. After completing baseline testing, there were 6 visits at which medication (placebo or D-cycloserine at 100 mg dose) was dispensed. Dosing was oral and twice weekly (Monday and Wednesday) throughout the study. The study design included one session per week (Friday) in which the drug was not dispensed. Volunteers received medication immediately preceding the robotic training sessions. Final examination was administered on Day 30. + indicates medication given and − indicates no medication given. RAP: robotic-assisted physiotherapy.
Figure 2
Figure 2
Robotic weighted score. Weighted scores on 6 times during which placebo or D-cycloserine (D-cycloserine) at 100 mg dose was dispensed. Across all subjects, mean weighted score on the (a) balloon game and (b) thera-pong improved significantly, from baseline to end of week 1, to week 2, and to week 3. However, there were no significant differences according to treatment group or interaction for any of these time intervals.

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