RESUMO
There are multiple available treatments to enhance stroke rehabilitation, although few interventions have confirmed significant clinical improvements on motor function in pivotal Randomized Clinical Trials. Development of large Randomized Clinical Trials is limited by several barriers and low enrollment rate is considered an important factor. Consequently, most of the evidence comes from small sample size studies, often leading to limited conclusions. According to the National Institute of Health (NIH), about 80% of clinical trials in the United States do not achieve their timelines, increasing research costs and postponing regulatory approval of new therapies. Given that the success of a Randomized Clinical Trial is dependent on enrolling an adequate number of subjects, effective strategies to enhance recruitment rates are highly desirable. In addition, given the resources and time limitations, it is important to understand which strategies are most cost-effective. In this manuscript, we summarize and discuss nine recruitment strategies used in an NIH R21 sponsored clinical trial, including medical records review and online advertising, among others. In addition, we developed an index to compare the time spent benefit of each approach and guide the allocation of the recruitment efforts. For this trial, online advertising and referral from health care professionals other than physicians were the strategies with greater time-benefit, leading to the largest number of stroke subjects enrolled.
RESUMO
Background. Although recent evidence has shown a new role of fluoxetine in motor rehabilitation, results are mixed. We conducted a randomized clinical trial to evaluate whether combining repetitive transcranial magnetic stimulation (rTMS) with fluoxetine increases upper limb motor function in stroke. Methods. Twenty-seven hemiparetic patients within 2 years of ischemic stroke were randomized into 3 groups: Combined (active rTMS + fluoxetine), Fluoxetine (sham rTMS + fluoxetine), or Placebo (sham rTMS + placebo fluoxetine). Participants received 18 sessions of 1-Hz rTMS in the unaffected primary motor cortex and 90 days of fluoxetine (20 mg/d). Motor function was assessed using Jebsen-Taylor Hand Function (JTHF) and Fugl-Meyer Assessment (FMA) scales. Corticospinal excitability was assessed with TMS. Results. After adjusting for time since stroke, there was significantly greater improvement in JTHF in the combined rTMS + fluoxetine group (mean improvement: -214.33 seconds) than in the placebo (-177.98 seconds, P = 0.005) and fluoxetine (-50.16 seconds, P < 0.001) groups. The fluoxetine group had less improvement than placebo on both scales (respectively, JTHF: -50.16 vs -117.98 seconds, P = 0.038; and FMA: 6.72 vs 15.55 points, P = 0.039), suggesting that fluoxetine possibly had detrimental effects. The unaffected hemisphere showed decreased intracortical inhibition in the combined and fluoxetine groups, and increased intracortical facilitation in the fluoxetine group. This facilitation was negatively correlated with motor function improvement (FMA, r2 = -0.398, P = 0.0395). Conclusion. Combined fluoxetine and rTMS treatment leads to better motor function in stroke than fluoxetine alone and placebo. Moreover, fluoxetine leads to smaller improvements than placebo, and fluoxetine's effects on intracortical facilitation suggest a potential diffuse mechanism that may hinder beneficial plasticity on motor recovery.
