Dose Escalation Upper Limb Rehabilitation in Stroke

Study Overview
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Brief Summary
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A phase 1, single-ascending dose clinical trial will be conducted. This study will be designed to test increasing doses of multimodal exercise in successive cohorts of six participants (cumulative 3 + 3 design)[22] (Figure 1). Maximum dose is reached when two or more participants experience DLT. DLT, dose-limiting tolerance. The 'dose' will be defined as the ability to reach a fixed maximal level of exercise (type, duration (including session length) in the first two weeks post-stroke without experiencing dose-limiting tolerance (DLT). DLT thresholds will be based on failure to complete more than 20% of prescribed 3-day rehabilitation dose due to pain, rate of perceived exertion, fatigue, or effort required. Rehabilitation and measurement sessions will be held at either at the Stroke or Geriatric Units at Campus Sint-Jan, Genk or at the rehabilitation unit at Sint-Barbara, Lanaken, with medical services on site. All participants will be monitored for fatigue and pain pre, during and at post-intervention daily. The researchers (PI of project [Dr Peter Hallet, ZOL] Postdoctoral Researcher [Dr Lisa Tedesco Triccas, UHasselt] and PhD/Masters Students [UHasselt) will conduct the clinical tests and will conduct the rehabilitation program.

Official Title
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Finding the Optimal Session Length of Upper Limb Rehabilitation of People With Moderate to Severe Upper Limb Sensorimotor Impairments After Acute Stroke: A Dose Escalation Study

Conditions
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Stroke

Intervention / Treatment
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* Other: upper limb rehabilitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: a first-ever unilateral, diagnosed stroke by a neurologist as defined by the World Health Organisation, been admitted to the acute hospital for rehabilitation, UL hemiparesis or hemiplegia with a ≥ trace of muscle contraction (≥grade 1 at wrist extensors measured by the MRC Scale and severely motor affected by score of 2 or 3 on item number 5 on the NIH Stroke Scale (NIHSS), the age of > 18 years and (e) the ability to provide informed consent. Exclusion Criteria: other neurological impairments that could interfere with the protocol such as multiple sclerosis and Parkinson's serious communication, cognitive and language deficits which might hamper the assessment (score of >1 on the command item of the NIHSS).

Ages Eligible for Study
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Minimum Age: 18 Years

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: participants with acute stroke<br>(a) a first-ever unilateral, diagnosed stroke by a neurologist as defined by the World Health Organisation, (b) been admitted to the acute hospital for rehabilitation, (c) Upper limb hemiparesis or hemiplegia with a trace of muscle contraction:≥grade 1 at shoulder (abductors or elevators) or wrist/finger extensors measured by the MRC Scale and a score of <61 on the Motricity Index and severely motor affected by score of 2 or 3 on item number 5 on the NIH Stroke Scale (NIHSS)[24], (d) the age of > 18 years and (e) the ability to provide informed consent. | Other: upper limb rehabilitation<br>* the intervention consisting of two components: a) Upper limb training protocol; b) Technology-assist training.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fugl-Meyer Assessment of Motor Recovery after Stroke | a stroke-specific, performance-based impairment index.The scale is comprised of five domains and there are 155 items in total (motor functioning, sensory functioning, balance, joint range motion, joint pain). Scoring is based on direct observation of performance. Scale items are scored on the basis of ability to complete the item using a 3-point ordinal scale where 0=cannot perform, 1=performs partially and 2=performs fully. The total possible scale score is 226. | baseline | 
| Fugl-Meyer Assessment of Motor Recovery after Stroke | a stroke-specific, performance-based impairment index.The scale is comprised of five domains and there are 155 items in total (motor functioning, sensory functioning, balance, joint range motion, joint pain). Scoring is based on direct observation of performance. Scale items are scored on the basis of ability to complete the item using a 3-point ordinal scale where 0=cannot perform, 1=performs partially and 2=performs fully. The total possible scale score is 226. | day 6 | 
| Fugl-Meyer Assessment of Motor Recovery after Stroke | a stroke-specific, performance-based impairment index.The scale is comprised of five domains and there are 155 items in total (motor functioning, sensory functioning, balance, joint range motion, joint pain). Scoring is based on direct observation of performance. Scale items are scored on the basis of ability to complete the item using a 3-point ordinal scale where 0=cannot perform, 1=performs partially and 2=performs fully. The total possible scale score is 226. | day 9 | 
| Fugl-Meyer Assessment of Motor Recovery after Stroke | a stroke-specific, performance-based impairment index.The scale is comprised of five domains and there are 155 items in total (motor functioning, sensory functioning, balance, joint range motion, joint pain). Scoring is based on direct observation of performance. Scale items are scored on the basis of ability to complete the item using a 3-point ordinal scale where 0=cannot perform, 1=performs partially and 2=performs fully. The total possible scale score is 226. | day 12 | 
| Fugl-Meyer Assessment of Motor Recovery after Stroke | a stroke-specific, performance-based impairment index.The scale is comprised of five domains and there are 155 items in total (motor functioning, sensory functioning, balance, joint range motion, joint pain). Scoring is based on direct observation of performance. Scale items are scored on the basis of ability to complete the item using a 3-point ordinal scale where 0=cannot perform, 1=performs partially and 2=performs fully. The total possible scale score is 226. | day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motricity index | Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength. | day 3 | 
| Motricity index | Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength. | day 4 | 
| Motricity index | Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength. | day 5 | 
| Motricity index | Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength. | day 6 | 
| Motricity index | Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength. | day 7 | 
| Motricity index | Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength. | day 8 | 
| Motricity index | Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength. | day 9 | 
| Motricity index | Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength. | day 10 | 
| Motricity index | Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength. | day 11 | 
| Motricity index | Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength. | day 12 | 
| Motricity index | Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength. | day 13 | 
| Motricity index | Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength. | day 14 | 
| Motricity index | Measurement of upper limb strength. The weighted score based on the ordinal 6 point scale of Medical Research Council was used to measure maximal isometric muscle strength. | day 15 | 
| Visual Analog Scale of Fatigue (VAS-f) | The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10). | day 3 | 
| Visual Analog Scale of Fatigue (VAS-f) | The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10). | day 4 | 
| Visual Analog Scale of Fatigue (VAS-f) | The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10). | day 5 | 
| Visual Analog Scale of Fatigue (VAS-f) | The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10). | day 6 | 
| Visual Analog Scale of Fatigue (VAS-f) | The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10). | day 7 | 
| Visual Analog Scale of Fatigue (VAS-f) | The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10). | day 8 | 
| Visual Analog Scale of Fatigue (VAS-f) | The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10). | day 9 | 
| Visual Analog Scale of Fatigue (VAS-f) | The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10). | day 10 | 
| Visual Analog Scale of Fatigue (VAS-f) | The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10). | day 11 | 
| Visual Analog Scale of Fatigue (VAS-f) | The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10). | day 12 | 
| Visual Analog Scale of Fatigue (VAS-f) | The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10). | day 13 | 
| Visual Analog Scale of Fatigue (VAS-f) | The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10). | day 14 | 
| Visual Analog Scale of Fatigue (VAS-f) | The scale consists of 18 items relating to the subjective experience of fatigue.Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10). | day 15 | 
| Borg RPE Scale | Measurement of physical activity intensity (6 to 20 scale) | day 3 | 
| Borg RPE Scale | Measurement of physical activity intensity (6 to 20 scale) | day 4 | 
| Borg RPE Scale | Measurement of physical activity intensity (6 to 20 scale) | day 5 | 
| Borg RPE Scale | Measurement of physical activity intensity (6 to 20 scale) | day 6 | 
| Borg RPE Scale | Measurement of physical activity intensity (6 to 20 scale) | day 7 | 
| Borg RPE Scale | Measurement of physical activity intensity (6 to 20 scale) | day 8 | 
| Borg RPE Scale | Measurement of physical activity intensity (6 to 20 scale) | day 9 | 
| Borg RPE Scale | Measurement of physical activity intensity (6 to 20 scale) | day 10 | 
| Borg RPE Scale | Measurement of physical activity intensity (6 to 20 scale) | day 11 | 
| Borg RPE Scale | Measurement of physical activity intensity (6 to 20 scale) | day 12 | 
| Borg RPE Scale | Measurement of physical activity intensity (6 to 20 scale) | day 13 | 
| Borg RPE Scale | Measurement of physical activity intensity (6 to 20 scale) | day 14 | 
| Borg RPE Scale | Measurement of physical activity intensity (6 to 20 scale) | day 15 | 
| Numeric rating scale pain | The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. no pain) to '10' representing the other pain extreme (e.g. pain as bad as you can imagine or worst pain imaginable) | day 3 | 
| Numeric rating scale pain | The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. no pain) to '10' representing the other pain extreme (e.g. pain as bad as you can imagine or worst pain imaginable) | day 4 | 
| Numeric rating scale pain | The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. no pain) to '10' representing the other pain extreme (e.g. pain as bad as you can imagine or worst pain imaginable) | day 5 | 
| Numeric rating scale pain | The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. no pain) to '10' representing the other pain extreme (e.g. pain as bad as you can imagine or worst pain imaginable) | day 6 | 
| Numeric rating scale pain | The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. no pain) to '10' representing the other pain extreme (e.g. pain as bad as you can imagine or worst pain imaginable) | day 7 | 
| Numeric rating scale pain | The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. no pain) to '10' representing the other pain extreme (e.g. pain as bad as you can imagine or worst pain imaginable) | day 8 | 
| Numeric rating scale pain | The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. no pain) to '10' representing the other pain extreme (e.g. pain as bad as you can imagine or worst pain imaginable) | day 9 | 
| Numeric rating scale pain | The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. no pain) to '10' representing the other pain extreme (e.g. pain as bad as you can imagine or worst pain imaginable) | day 10 | 
| Numeric rating scale pain | The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. no pain) to '10' representing the other pain extreme (e.g. pain as bad as you can imagine or worst pain imaginable) | day 11 | 
| Numeric rating scale pain | The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. no pain) to '10' representing the other pain extreme (e.g. pain as bad as you can imagine or worst pain imaginable) | day 12 | 
| Numeric rating scale pain | The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. no pain) to '10' representing the other pain extreme (e.g. pain as bad as you can imagine or worst pain imaginable) | day 13 | 
| Numeric rating scale pain | The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. no pain) to '10' representing the other pain extreme (e.g. pain as bad as you can imagine or worst pain imaginable) | day 14 | 
| Numeric rating scale pain | The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. no pain) to '10' representing the other pain extreme (e.g. pain as bad as you can imagine or worst pain imaginable) | day 15 |