Safety and Effectiveness of Botulinum Toxin in Elderly Patients With Dementia and Muscle Stiffness

Study Overview
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Brief Summary
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Aim of the study is to perform a pilot study to assess the impact of Botulinum toxin on muscle tone, and caregiver burden in individuals who are cognitively impaired and who are fully dependent. The primary objective is to confirm proof of principle that paratonic rigidity and the consequences associated with it can be reduced with injection of Botulinum toxin injections resulting in reduced care-giver burden. The secondary objectives are to determine optimal time points for evaluation of efficacy in this patient population and whether the time period is sufficient for washout of Botulinum toxin effect; determine most salient and sensitive outcome measures; identify obstacles in data gathering; and lastly, to determine feasibility of battery of assessments in this pilot study.

Official Title
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A Randomized, Placebo Controlled Trial of Botulinum Toxin for Paratonic Rigidity in People With Advanced Cognitive Impairment

Conditions
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Dementia, Paratonia

Intervention / Treatment
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* Drug: Botulinum Toxin
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe cognitive impairment (complete dependency in all activities of daily living (ADLs) Diagnosis of Alzheimer's disease, vascular dementia,or frontotemporal dementia Score> 3 on the paratonic assessment instrument, with paratonic rigidity in an arm(s) interfering in the provision of care Exclusion Criteria: Alternate etiologies for increased tone Botulinum toxin 6 months preceding the study
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Saline<br>Saline injection up to 5 cc in arm with paratonia (one time injection) | Drug: Saline<br> <br> |
| Active Comparator: Botulinum Toxin<br>Up to 300 U (5 cc) of Botulinum toxin diluted 2:1 (2 cc per 100 U of Botulinum toxin) (one time injection) | Drug: Botulinum Toxin<br> <br> * Other names: Xeomin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact on care-giver burden | Impact on caregiver burden in providing upper extremity care. Measured by the Carer Burden Scale which includes four items (cleaning the palm, cutting the fingernails, dressing, cleaning under the armpit). Each item rated on five point Likert scale (no difficulty to cannot do task). | 6 weeks for primary outcome, 32 weeks for entire study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analogue Scale | Completed by the professional caregiver that is caring for the patient to assess perception of ease of caregiving. Consists of 100 mm line with anchors of 0 giving care to the residents is very difficult and 100 giving care to the residents is very easy | 6 weeks for secondary outcome, 32 weeks for entire study | 
| Joint angle measurement | Joint angle measurements were used reflecting range of motion. Used as a surrogate measure for severity of paratonia | 6 weeks for secondary outcome, 32 weeks for entire study | 
| Pain | Pain Assessment in Advanced Dementia (PAINAD) Scale used to evaluate correlates of pain and determine whether Botulinum toxin treatment reduces discomfort of morning care. Consists of 5 items (breathing, negative vocalization, facial expression, body language and consolability), scored on a 0-2 point scale and then summed to arrive at a total scale. | 6 weeks for secondary outcome, 32 weeks for entire study | 
| Global Assessment | Overall response to treatment evaluated by study investigator and by professional caregiver caring for patient using the global assessment scale. A score of -4 indicates very marked worsening, 0 no change, and +4 very marked improvement. | 6 weeks for secondary outcome, 32 weeks for entire study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dementia, Paratonia, Caregiver Burden, Botulinum toxin