Combinational Rehabilitative Therapy and Functional Brain Imaging for Patients Recovering From Motor Stroke

NCT02073773 | Completed Phase 3 DMC

• 1 other identifier: CIRB 2013/323/D
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The present proposal aims to assess whether a combined rehabilitation approach using virtual reality based therapy with motivational feedback, levodopa for pharmacotherapy and standard rehabilitative occupational therapy and physiotherapy will lead to signifcantly better outcomes for stroke recovery. It is a randomised controlled trial with blinding of the assessors only. It will be preceeded by a Phase 1 pilot trial of the VR physiotherapy and standard therapy only. Recruited in-patient rehabilitation ward patients who have recently suffered stroke will be randomized, through a computer-based random number generator, to either one of two treatment arms:

1. 1.Control occupational therapy + pharmacotherapy for 2 weeks
2. 2.Assisted Virtual-Reality physiotherapy + pharmacotherapy for 2 weeks

Conditions

Ischaemic Stroke

Keywords

stroke, virtual reality based therapy

Outcome Measures

Primary Outcomes (1)

• Changes in the Fugl Meyer Upper Limb score at the start and end of the two weeks trial period

  Fugl Meyer Upper Extremity Scale (FM) - a clinical assessment of upper limb tone, power and movement.

  At the start and end of the 2 weeks period of trial therapy

Secondary Outcomes (2)

• Changes in the Action Research Arm Test (ARAT)

  At the start and end of the 2 weeks period of trial therapy

• Changes in the Functional independence measure score

  At the start and end of the 2 weeks therapy period

Other Outcomes (2)

• Changes in Kinematic data of affected upper limb movement

  At the start and end of the 2 weeks trial period

• changes in resting state functional MRI imaging of the brain

  At the start and end of the 2 weeks trial period

Study Arms (2)

Virtual Reality based therapy, levodopa

EXPERIMENTAL

The VR therapy session consists of the subject interacting with a computer-based program in which they guide an avatar to gather items by using flexion and extension gestures of the affected upper limb. VR therapy sessions will last for 15-30 minutes depending on the subject's tolerance and participation. For patients who are unable to overcome gravity fully, they can still participate in this therapy by resting their arm on a table. Patients will receive a single dose of 100mg levodopa in combination with benserazide 2-3 hours before each additional Occupational therapy session or VR therapy session depending on the assigned group.

Drug: Levodopa; Other: Virtual Reality based therapy

occupational therapy, levodopa

ACTIVE COMPARATOR

The control group will receive and additional half an hour per working day of standard occupational therapy. Patients will receive a single dose of 100mg levodopa in combination with benserazide 2-3 hours before each additional Occupational therapy session or VR therapy session depending on the assigned group.

Drug: Levodopa

Interventions

Levodopa DRUG

Levodopa 100mg with benserazide 25mg will be administered 3 hours prior to the start of the daily PT/OT session to maximize its pharmacokinetic window ie. blood plasma levels in the narrow window during which functional rewiring of neural circuits is thought to occur. Levodopa at the lowest available dose (100mg P.O qd) has been shown to improve motor function of stroke patients and their corresponding quality of life. The treatment proposed can be incorporated into their daily rehabilitation routine. Early intervention (within 7-21 days of the infarct) raises the chance for neuroplasticity and improved recovery of their motor function in the short and long run. Levodopa has been proven to be safe to be used in stroke patients (Lancet. 2001 Sep 8;358(9284):787-90., Arch Phys Med Rehabil. 2008 Sep;89(9):1633-41.), however, the side effects of this medication may include nausea, unusual tiredness, dizziness, excessive watering of mouth.

Also known as: Madopar

Virtual Reality based therapy, levodopa; occupational therapy, levodopa

Virtual Reality based therapy OTHER

The VR therapy session consists of the subject interacting with a computer-based program in which they guide an avatar to gather items by using flexion and extension gestures of the affected upper limb. VR therapy sessions will last for 15-30 minutes depending on the subject's tolerance and participation. For patients who are unable to overcome gravity fully, they can still participate in this therapy by resting their arm on a table.

Virtual Reality based therapy, levodopa

Eligibility Criteria

• Age: 25 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 25-99yrs
• Right-handed
• Cognitively coherent, able to provide informed consent (MMSE \>25)
• Newly diagnosed, first episode ischemic stroke in the past 2-21 days
• Motor score: Strength of 2-3 out of 5 on affected side upper limb

You may not qualify if:

• Declined consent to participate in the study
• Cognitive impairment or significant aphasia with inability to understand study requirements and inability to participate in therapy
• Other neurological or physical ailments with pre-existing motor weakness
• Haemorrhagic stroke
• Patient due to undergo significant medical interventions such as carotid endarthrectomy
• Patients on neuroactive agents prior to the stroke such as antidepressants
• Hypersensitivity to benserazide, levodopa, sympathomimetics, or any component of the formulation
• Use of MAO inhibitors within the last 14 days
• Patients with clinical or laboratory evidence of uncompensated cardiovascular, endocrine, renal, hepatic, hematologic, or pulmonary disease
• Patients with decompensated endocrine, renal, hepatic, cardiac disorders, psychiatric disorders, narrow-angle glaucoma, or closed-angle glaucoma;
• Patients \<25 years of age (due to possibility of skeletal abnormalities from benserazide)
• Pregnancy or use in women of childbearing potential without adequate contraception.

Sponsors & Collaborators

• Singapore General Hospital: lead
• Singapore University of Technology and Design: collaborator

Study Sites (1)

Singapore General Hospital

Singapore, SIngapore, 169608, Singapore

Location

MeSH Terms

Conditions

Ischemic Stroke; Stroke

Interventions

Levodopa; benserazide, levodopa drug combination

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine

Study Officials

• Yee S NG, MBBS, MRCP

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2014
• First Posted: February 27, 2014
• Study Start: January 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: February 10, 2017

Record last verified: 2017-02

Locations

SG (1)