Clinical trial NCT05369533: Dopaminergic Enhancement of Rehabilitation Therapy Early After Stroke
Official title: Dopaminergic Enhancement of Rehabilitation Therapy Early After Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Stroke
Keywords: stroke
rehabilitation
telehealth
dopamine
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
First posted: 2022-05-11
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients are randomized to TR + placebo, TR + Sinemet, or usual care
Primary purpose: TREATMENT

Brief summary: This study explores the effects of telerehabilitation and a study medication on rehabilitation outcomes in patients with stroke resulting in arm weakness. Patients with arm weakness due to a stroke that happened in the past 30 days will be randomized into one of three groups: \[1\] TR and placebo (a sugar pill) on top of usual care; \[2\] TR and a medication (Sinemet 25/100) on top of usual care; \[3\] or usual care alone (no TR and no pill, but people in this group will be offered TR once the study is done). TR consists of 70 minutes/day of activities targeting arm function, 6 days a week for 6 weeks.

Detailed description: This is a randomized, double-blind, placebo-controlled study that involves the use of telerehabilitation to deliver additional therapy for persons with stroke. Participants with arm weakness due to a stroke in the past 30 days will be randomized into one of three groups: (1) TR + Sinemet on top of usual care, (2) TR + placebo (sugar pill) on top of usual care, or (3) usual care only (no TR, no pill). The hypothesis of this study is patients receiving TR will have significantly greater recovery of arm function compared to patients receiving usual care. In addition, Sinemet is hypothesized to significantly enhancing this improvement.

Study participation will last up to 3 months and includes 4 in-person visits. At these visits, patients will undergo a battery of assessments including arm function, a single MRI scan of the brain, and blood draw for genotyping. Patients undergoing TR will receive arm motor training, which consists of 36 sessions of of assigned exercises, games, and stroke education; these are 70 minutes in length and take 6 days a week over 6-8 weeks. Subjects receiving TR will take a pill (Sinemet or placebo) prior to the TR training for the first 18 TR sessions; TR subjects will also continue usual care. Patients in the usual care group will not engage in TR or take a study pill, but will instead continue all of the therapies recommended by their medical team. At the end of the study, participants in the usual care group will be offered TR.

Eligibility criteria: INCLUSION CRITERIA

1. Age 18 years or older
2. Stroke that has been radiologically verified and has time of onset 30 days or less from the time of randomization
3. ARAT score of \<32 (out of 57) at Visit 1
4. At Visit 1, either

   1. BBT score with affected arm is at least 1 block in 60 seconds OR
   2. There is a visible flicker in each of the following movements with gravity eliminated: wrist extension and finger flexion
5. At Visit 1, either

   1. The range of motion against gravity must be ≥45 degrees in both the paretic shoulder and elbow OR
   2. the patient must be able to use at least 3 different telerehab system input devices
6. Informed consent and behavioral contract signed by the subject (i.e., no surrogate consent)

EXCLUSION CRITERIA

1. A major, active, coexistent neurological or psychiatric disease (e.g., alcoholism or dementia)
2. Major medical disorder that reduces subject's ability to comply with study procedures
3. Severe depression, defined as CES-D score \>24 at screening visit
4. Significant cognitive impairment, defined as presence of either

   1. Montreal Cognitive Assessment (MoCA) score \<22 OR
   2. Trail Making Test: Part A score ≤14
   3. Note that lower scores may be permitted if due to aphasia and if the patient is specifically allowed by Dr. Cramer
5. Deficits in communication that interfere with reasonable study participation
6. Lacking visual acuity, with or without corrective lens, of 20/50 or better in at least one eye
7. Life expectancy \<6 months
8. Pregnant
9. Botox to arms, legs or trunk in the preceding 4 months, or expectation that Botox will be administered to the arm, leg or trunk within 3 months of study enrollment
10. Unable to successfully perform all 3 rehabilitation exercise test examples
11. Unable or unwilling to perform study procedures/therapy or attend study visits, or expectation of noncompliance with study procedures/therapy
12. Non-English or non-Spanish speaking, such that subject does not speak either language sufficiently to comply with study procedures
13. Isolation due to active COVID-19
14. Any contraindication to L-Dopa:

    1. Patient is currently taking a monoamine oxidase inhibitor; if the patient took such a drug in the past, it must be discontinued at least two weeks prior to study enrollment
    2. Known hypersensitivity to any component of Sinemet
    3. Narrow-angle glaucoma; if wide-angle glaucoma is present, the patient can only be enrolled with explicit written approval from their ophthalmologist
    4. History of melanoma or suspected melanoma
    5. Patient is currently taking phenytoin, papaverine, isoniazid, or a dopamine D2 receptor antagonist (such as a phenothiazine, butyrophenone, or risperidone)
    6. Currently taking a direct dopaminergic agonist
15. Expectation that subject will not have single domicile address during 6 weeks of therapy that has either Verizon wireless reception or a home WiFi network and that has space for TR system, and is within 30 miles of Cal Rehab

Primary outcomes:
measure: Change in Action Research Arm Test Score From Baseline to 3 Months
timeFrame: Measured at baseline and 3 months later
Secondary outcomes:
measure: Change in Arm Motor Fugl-Meyer Scale From Baseline to 3 Months
timeFrame: Measured at baseline and 3 months later
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: California Rehabilitation Institute
state: California
Study officials:
affiliation: University of California, Los Angeles
name: Steven Cramer
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dodakian L, McKenzie AL, Le V, See J, Pearson-Fuhrhop K, Burke Quinlan E, Zhou RJ, Augsberger R, Tran XA, Friedman N, Reinkensmeyer DJ, Cramer SC. A Home-Based Telerehabilitation Program for Patients With Stroke. Neurorehabil Neural Repair. 2017 Oct-Nov;31(10-11):923-933. doi: 10.1177/1545968317733818. Epub 2017 Oct 26.
citation: Chen Y, Abel KT, Janecek JT, Chen Y, Zheng K, Cramer SC. Home-based technologies for stroke rehabilitation: A systematic review. Int J Med Inform. 2019 Mar;123:11-22. doi: 10.1016/j.ijmedinf.2018.12.001. Epub 2018 Dec 11.
citation: Cramer SC, Dodakian L, Le V, See J, Augsburger R, McKenzie A, Zhou RJ, Chiu NL, Heckhausen J, Cassidy JM, Scacchi W, Smith MT, Barrett AM, Knutson J, Edwards D, Putrino D, Agrawal K, Ngo K, Roth EJ, Tirschwell DL, Woodbury ML, Zafonte R, Zhao W, Spilker J, Wolf SL, Broderick JP, Janis S; National Institutes of Health StrokeNet Telerehab Investigators. Efficacy of Home-Based Telerehabilitation vs In-Clinic Therapy for Adults After Stroke: A Randomized Clinical Trial. JAMA Neurol. 2019 Sep 1;76(9):1079-1087. doi: 10.1001/jamaneurol.2019.1604.
citation: Chen Y, Chen Y, Zheng K, Dodakian L, See J, Zhou R, Chiu N, Augsburger R, McKenzie A, Cramer SC. A qualitative study on user acceptance of a home-based stroke telerehabilitation system. Top Stroke Rehabil. 2020 Mar;27(2):81-92. doi: 10.1080/10749357.2019.1683792. Epub 2019 Nov 4.
citation: Cramer SC, Dodakian L, Le V, McKenzie A, See J, Augsburger R, Zhou RJ, Raefsky SM, Nguyen T, Vanderschelden B, Wong G, Bandak D, Nazarzai L, Dhand A, Scacchi W, Heckhausen J. A Feasibility Study of Expanded Home-Based Telerehabilitation After Stroke. Front Neurol. 2021 Feb 3;11:611453. doi: 10.3389/fneur.2020.611453. eCollection 2020.
citation: Paik SM, Cramer SC. Predicting motor gains with home-based telerehabilitation after stroke. J Telemed Telecare. 2023 Dec;29(10):799-807. doi: 10.1177/1357633X211023353. Epub 2021 Jun 22.
citation: Pearson-Fuhrhop KM, Cramer SC. Pharmacogenetics of neural injury recovery. Pharmacogenomics. 2013 Oct;14(13):1635-43. doi: 10.2217/pgs.13.152.