A randomized, placebo controlled pilot trial of botulinum toxin for paratonic rigidity in people with advanced cognitive impairment

Abstract

Objective: Evaluate safety and efficacy of Incobotulinumtoxin A in elderly patients with dementia and paratonia.

Setting: University-affiliated hospital, spasticity management Clinic.

Participants: Ten subjects were enrolled.

Inclusion criteria: 1) severe cognitive impairment 2) diagnosis of Alzheimer's disease, vascular dementia, or frontotemporal dementia, and 3) score >3 on the paratonic assessment instrument, with posture in an arm(s) interfering with provision of care.

Exclusion criteria: 1) alternate etiologies for increased tone and 2) injection with botulinum toxin within the 6 months preceding the study.

Design: Single center, randomized, double blind, placebo-controlled, crossover trial with two treatment cycles of 16 weeks. Assessments occurred at 2, 6, 12 and16 weeks following injections. Subjects received up to 300 U of Incobotulinumtoxin A in arm(s).

Primary and secondary outcome measures: Primary outcome measure was the modified caregiver burden scale (mCBS); exploratory secondary outcome measures were also performed. Analysis of variance and mixed modeling techniques were used to evaluate treatment effects.

Results: Incobotulinumtoxin A treatment produced significant improvement in mCBS total score -1.11 (-2.04 to -0.18) (Treatment effect and 95% CI), dressing sub-score -0.36 (-0.59 to 0.12), and cleaning under the left and right armpits sub-score -0.5 (-0.96 to -0.04), -0.41 (-0.79 to -0.04) respectively. PROM in the left and right elbow increased by 27.67 degrees (13.32-42.02) and 22.07 degrees (9.76-34.39) respectively. PROM in the left and right shoulder increased by 11.92 degrees (5.46-18.38) and 8.58 degrees (3.73-13.43) respectively. No significant treatment effect was found for GAS, VAS and PAINAD scales or change in time to perform care. No adverse drug reactions occurred.

Conclusions: Administration of Incobotulinumtoxin A in elderly people with advanced dementia and paratonia may be an efficacious and safe treatment to increase range of motion and reduce functional burden. Further studies are needed to confirm results.

Trial registration: ClinicalTrials.Gov NCT02212119.

Conflict of interest statement

Competing Interests: The principal investigator has received consulting honoraria from Merz Pharmaceuticals GmbH. None of the other authors have a conflict of interest, financial or otherwise. This does not alter the authors’ adherence to all PLoS ONE policies on sharing data and materials.

Figures

Figure 1. Study flow diagram.

Figure 2. mCarer Burden Scale (mCBS) in each subject treated with Incobotulinumtoxin A (□) and Placebo (Δ).

Figure 3. Passive range of motion (PROM) following Incobotulinumtoxin A injections (□) and Placebo (Δ) treatments for: A) Shoulder B) Elbow C) Fingers.