Intravenous amantadine for freezing of gait resistant to dopaminergic therapy: a randomized, double-blind, placebo-controlled, cross-over clinical trial

Young Eun Kim, Ji Young Yun, Hui June Yang, Han-Joon Kim, Namyi Gu, Seo Hyun Yoon, Joo-Youn Cho, Beom S Jeon, Young Eun Kim, Ji Young Yun, Hui June Yang, Han-Joon Kim, Namyi Gu, Seo Hyun Yoon, Joo-Youn Cho, Beom S Jeon

Abstract

Background: Freezing of gait (FOG) is one of the most disabling symptoms in Parkinsonism. Open-label studies have suggested that intravenous (IV) amantadine is effective against FOG resistant to dopaminergic therapy in Parkinson's disease (PD). We evaluated the efficacy of IV amantadine on FOG resistant to dopaminergic therapy.

Methodology/principal findings: This was a randomized, double-blind, placebo-controlled, cross-over study on IV amantadine. The placebo (normal saline) and amantadine (400 mg/day) were injected for 2 days with a 52-hour washout period. The instruments for the outcome measures were the Freezing of Gait Questionnaire (FOGQ), Unified Parkinson's disease rating Scale (UPDRS), and the duration of the 4×10 m walking test. The placebo arm was compared to the amantadine arm. Ten patients were enrolled but two patients withdrew, one from each arm. The FOGQ and UPDRS scores and the duration of the 4×10 m walking test improved in both arms compared to the baseline (P<0.05 in all). However, there were no differences in these values between the amantadine arm and placebo arm (P = 0.368, P = 0.583, P = 0.206, respectively). Follow-up measures 2 weeks after discharge in an open-label study showed the beneficial effects of an amantadine tablet on FOG (FOGQ, P = 0.018; UPDRS, P = 0.012 respectively).

Conclusions/significance: This double blind, placebo-controlled study did not show the efficacy of IV amantadine on FOG when compared with the placebo. This study provides Class II evidence due to small sample size for the lack of benefit of IV amantadine on FOG resistant to dopaminergic therapy

Trial registration: Clinicaltrials.gov NCT01313819.

Conflict of interest statement

Competing Interests: This work was funded by the Han Wha Pharm Co. Ltd. This dose not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. CONSORT diagram.
Figure 1. CONSORT diagram.
Figure 2. Timeline of drug and clinical…
Figure 2. Timeline of drug and clinical assessments.

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