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Improving Holding Function of the Hemiplegic Hand

Improving Holding Function of the Hemiplegic Hand With Chemodenervation

Status
Completed
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT02459951
Enrollment
10
Registered
2015-06-02
Start date
2015-07-31
Completion date
2017-04-30
Last updated
2019-07-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Stroke

Keywords

Muscle Spasticity, Botox A, Upper limb hemiplegia

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.

Interventions

OTHERclenched fist

Observation of performance on a standardized behavioral task pre- and post- administration of Botox A in the context of routine care. Clinical assessment and judgment will be used to determine dosing and which muscles contribute to the hand deformities of a given participant.

Sponsors

Allergan
CollaboratorINDUSTRY
Nathaniel Mayer
Lead SponsorOTHER

Study design

Observational model
CASE_ONLY
Time perspective
PROSPECTIVE

Eligibility

Sex/Gender
ALL
Age
35 Years to 80 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Geometric Ratios of Log-transformed Transit Timedays post-injection evaluation (mean 26 days; range 21-30 days)Time (log-transformed) required for contralateral hand to insert a plastic cylinder successfully into the hemiplegic clenched fist AND assessed at Pre-injection baseline 2 and a Post-injection session expressed as a geometric mean ratio of these sessions. (Success is defined by a hold of 5 secs or more). Geometric mean ratios are calculated for each of 5 cylinder sizes (A-E)

Secondary

MeasureTime frameDescription
Fraction of Successful Holds for Each Evaluation Sessiondays between two baseline evaluations (mean 6; range 2-14) and days post-injection evaluation (mean 26; range 21-30)fraction of successful holds for each evaluation session (Pre1, Pre2, and Post)
Ratio of Successful Holdsdays between two baseline evaluations (mean 6; range 2-14) and days post-injection evaluation (mean 26; range 21-30)ratio of successful holds post/pre1, post/pre2 or pre1/pre2

Other

MeasureTime frameDescription
Modified Ashworth Score (MAS)days between two baseline evaluations (mean 6; range 2-14) and days post-injection evaluation (mean 26; range 21-30)A clinical ordinal measure of resistance to passive stretch of a limb on a scale of 0-4 with higher scores representing greater resistance

Participant flow

Participants by arm

ArmCount
Hemiplegic Clenched Fist
Adult participants with upper limb hemiparesis secondary to stroke and greater than 12 months duration. Medical determination that .botulinum toxin injections are indicated for treatment of spasticity. clenched fist: Observation of performance on a standardized behavioral task pre- and post- administration of Botox A in the context of routine care. Clinical assessment and judgment will be used to determine dosing and which muscles contribute to the hand deformities of a given participant.
9
Total9

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyUnable to meet holding requirement1

Baseline characteristics

CharacteristicHemiplegic Clenched Fist
Age, Continuous61 years
days between the two baseline evaluations6 days
days post injection evaluation26 days
dominant hand is affected4 Participants
Fugl-Meyer Assessment (upper limb motor score only)24 units on a scale
Months post stroke64 months
Race and Ethnicity Not Collected— Participants
Region of Enrollment
United States
9 participants
Sex: Female, Male
Female
5 Participants
Sex: Female, Male
Male
4 Participants
Visual Neglect0 Participants
Weinstein Enhanced Sensory Test (West)4.42 units on a scale

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
0 / 9
other
Total, other adverse events
0 / 9
serious
Total, serious adverse events
0 / 9

Outcome results

Primary

Geometric Ratios of Log-transformed Transit Time

Time (log-transformed) required for contralateral hand to insert a plastic cylinder successfully into the hemiplegic clenched fist AND assessed at Pre-injection baseline 2 and a Post-injection session expressed as a geometric mean ratio of these sessions. (Success is defined by a hold of 5 secs or more). Geometric mean ratios are calculated for each of 5 cylinder sizes (A-E)

Time frame: days post-injection evaluation (mean 26 days; range 21-30 days)

ArmMeasureGroupValue (GEOMETRIC_MEAN)
Hemiplegic Clenched FistGeometric Ratios of Log-transformed Transit Timecylinder A (.5 diameter)1.19 dimensionless ratio
Hemiplegic Clenched FistGeometric Ratios of Log-transformed Transit Timecylinder B (1 diameter)1.07 dimensionless ratio
Hemiplegic Clenched FistGeometric Ratios of Log-transformed Transit Timecylinder C (1.5 diameter)0.79 dimensionless ratio
Hemiplegic Clenched FistGeometric Ratios of Log-transformed Transit Timecylinder D (2 diameter)0.72 dimensionless ratio
Hemiplegic Clenched FistGeometric Ratios of Log-transformed Transit Timecylinder E (2.5 diameter)0.66 dimensionless ratio
p-value: 0.059Regression, Logistic
p-value: 0.465Regression, Logistic
p-value: 0.022Regression, Logistic
p-value: 0.004Regression, Logistic
p-value: 0.002Regression, Logistic
Secondary

Fraction of Successful Holds for Each Evaluation Session

fraction of successful holds for each evaluation session (Pre1, Pre2, and Post)

Time frame: days between two baseline evaluations (mean 6; range 2-14) and days post-injection evaluation (mean 26; range 21-30)

ArmMeasureGroupValue (MEAN)
Hemiplegic Clenched FistFraction of Successful Holds for Each Evaluation Sessionpost injection.67 fraction of successful holds
Hemiplegic Clenched FistFraction of Successful Holds for Each Evaluation Sessionpre 1 baseline.51 fraction of successful holds
Hemiplegic Clenched FistFraction of Successful Holds for Each Evaluation Sessionpre2 baseline.53 fraction of successful holds
Secondary

Ratio of Successful Holds

ratio of successful holds post/pre1, post/pre2 or pre1/pre2

Time frame: days between two baseline evaluations (mean 6; range 2-14) and days post-injection evaluation (mean 26; range 21-30)

ArmMeasureGroupValue (MEAN)
Hemiplegic Clenched FistRatio of Successful Holdspost vs. pre11.31 ratio
Hemiplegic Clenched FistRatio of Successful Holdspost vs pre21.26 ratio
Hemiplegic Clenched FistRatio of Successful Holdspre1 vs pre2.96 ratio
Other Pre-specified

Modified Ashworth Score (MAS)

A clinical ordinal measure of resistance to passive stretch of a limb on a scale of 0-4 with higher scores representing greater resistance

Time frame: days between two baseline evaluations (mean 6; range 2-14) and days post-injection evaluation (mean 26; range 21-30)

ArmMeasureGroupValue (MEDIAN)
Hemiplegic Clenched FistModified Ashworth Score (MAS)Pre2 vs Pre10 units on a scale
Hemiplegic Clenched FistModified Ashworth Score (MAS)Post vs. Pre1-2 units on a scale
Hemiplegic Clenched FistModified Ashworth Score (MAS)Post vs. Pre2-2 units on a scale

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026