Clinical trial NCT02459951: Improving Holding Function of the Hemiplegic Hand
Official title: Improving Holding Function of the Hemiplegic Hand With Chemodenervation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Stroke
Keywords: Muscle Spasticity
Botox A
Upper limb hemiplegia
Lead sponsor: Albert Einstein Healthcare Network
Sponsor class: OTHER
Collaborators: name: Allergan
First posted: 2015-06-02
Enrollment: 10
Sex: ALL
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients who are clinically appropriate for Botox A injection to treat upper limb spasticity due to stroke

Brief summary: Relevant to patients with spastic hemiparesis in the hand and upper limb, this pilot project proposes to measure the effects of botulinum toxin injections through observation of performance on a functional task known as 'hand as a holder'. This task requires the person with hemiplegia to insert an object into the affected hand and hold it independently.

The project aims to demonstrate reliability and validity of a digital video method that will be used to measure 'insertion time'. It also aims to establish initial statistical support for improved object insertion time into the hemiplegic clenched fist after Botox A injections.

Detailed description: Holding is an everyday hand function, objects entering the hand radially, frontally, ulnarly or in-between the finger spaces. After a stroke, the hand of a person with hemiplegia typically lacks voluntary finger extension that opens the hand. Simultaneously, the hand is also subjected to involuntary contraction of finger flexor muscles that close the hand, resulting in clenched fist and thumb-in-palm deformities. Despite these typical hemiplegic configurations, persons with stroke may be able to insert an object into the hand by wiggling and pushing it into the hemiplegic hand with their uninvolved hand, though struggle is often present and failure is frequent. In the hemiplegic patient, a common driver of clenched fist and thumb-in-palm configurations is excessive involuntary neural activation of finger and thumb flexors, compounded by impaired or absent voluntary finger extension. Excessive finger and thumb flexor contractions have been variously ascribed to involuntary phenomena such as spasticity, spastic dystonia, co-contraction, associated reactions and others. For the investigators purpose here, these involuntary phenomena generate contractile tension in hand and thumb muscles that choke the hand's potential to function as a holder of objects as described above.

The underlying rationale of this project is to examine whether hemiplegic 'hand as a holder' function can be improved by weakening involuntary muscle contractions that generate clenched fist and thumb in palm using the neuromuscular blocking properties of Botox A. The investigators hypothesize that 'hand as a holder' function will improve after chemodenervation of relevant finger, thumb and wrist muscles selected by clinical examination.

Nine subjects will be enrolled. Baseline observations will be made on two occasions prior to Botox A injection and outcomes measured four weeks later. A digital video method will be used to measure 'insertion time' at all-time points. Given the importance of the relationship between "statistically significant" research results and "clinically significant", person-oriented, functional improvement, the investigators also hypothesize that experienced clinicians will independently rate the performance of object insertion into the clenched fist as globally better after chemodenervation.

Eligibility criteria: Inclusion Criteria:

* patients who are clinically appropriate for treatment of upper limb spasticity due to stroke with Botox A injections ;
* adults up to age 80, women must be post-menopausal or are medically unable to conceive (as determined from their medical records), men must be at least age 35
* documented anemic or hemorrhagic unilateral (right or left) hemiplegic stroke, with 1 year or more prior to enrollment
* able to understand verbal and visual instructions and demonstrations regarding the protocol
* a resting wrist angle equal to or less than 0
* spasticity is present in finger flexors and thumb coupled with marked voluntary paresis of finger extension (no finger has more than half range of active extension at any joint). By squeezing the examiner's finger, participants will have demonstrated, at least, some detectable voluntary contraction of finger flexors; impaired sensation is acceptable but participants must be aware that they are holding something, as tested clinically;
* at least two finger flexors with an Ashworth score = 3;
* moderate motor severity as defined by an upper limb Fugl-Meyer motor scores between 21-50
* normal joint capsule without contractures as determined by clinical exam; participant may have tightness/shortening of extrinsic finger flexors but composite extension of wrist and fingers comes to at least neutral (i.e. fingers and wrist can be brought to neutral position simultaneously).

Exclusion Criteria:

* profound sensory loss/absent touch sensation
* known hypersensitivity/allergy to Botox A
* acute illness or unresolved medical/psychiatric conditions at time of assessment
* symptomatic lung disease and compromised respiratory status; muscle-weakening neurological disorders known to increase drug-related risk \[e.g. amyotrophic lateral sclerosis (ALS), myasthenia gravis, Lambert-Eaton syndrome, or motor neuropathy\]
* infection in the area where the study drug should be injected
* pregnancy or breast-feeding;
* participant had Botox injections less than 4 months previously
* clenched fist associated with tenodesis of an extended wrist i.e. resting position of wrist is \> 0 degrees

Primary outcomes:
measure: Geometric Ratios of Log-transformed Transit Time
timeFrame: days post-injection evaluation (mean 26 days; range 21-30 days)
Secondary outcomes:
measure: Fraction of Successful Holds for Each Evaluation Session
timeFrame: days between two baseline evaluations (mean 6; range 2-14) and days post-injection evaluation (mean 26; range 21-30)
measure: Ratio of Successful Holds
timeFrame: days between two baseline evaluations (mean 6; range 2-14) and days post-injection evaluation (mean 26; range 21-30)
Other outcomes:
measure: Modified Ashworth Score (MAS)
timeFrame: days between two baseline evaluations (mean 6; range 2-14) and days post-injection evaluation (mean 26; range 21-30)
Locations:
Study officials:
affiliation: Albert Einstein Healthcare Network
name: Nathaniel Mayer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mayer NH, Ferraro M, Pauloski-Hunt D, Chervoneva I. Capacity for Hand-as-a-Holder Function of the Spastic Combination Hand: A Proof-of-Concept Study. Am J Phys Med Rehabil. 2022 Mar 1;101(3):298-302. doi: 10.1097/PHM.0000000000001834.