Clinical trial NCT06291480: Music Therapy After Stroke (Subacute Phase)
Official title: Music Therapy After Stroke (Subacute Phase): Assessing the Impact of Motivation and Neuroplasticity on Recovery of Upper-limb Impairment and Attention Deficits
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Stroke (CVA) or TIA
Stroke/Brain Attack
Keywords: Music Therapy
Neurologic Music Therapy
Movement rehabilitation
Cognitive rehabilitation
Motivation
Lead sponsor: Universiteit Leiden
Sponsor class: OTHER
Collaborators: name: Amstelring
First posted: 2024-03-04
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Intervention period compared to care as usual in cross-over design.
Primary purpose: TREATMENT

Brief summary: The goal of this longitudinal, single-subject study is to investigate the role of motivation in music therapy for stroke patients within the subacute phase, who experience upper limb and/or attention deficits. The main questions it aims to answer are:

* Does music therapy increase patient's motivation to rehabilitate?
* Do increases in motivation correlate with functional improvements, in particular upper limb and/or attention skills?

Participants will receive up to 9 music therapy sessions within 3-5 weeks, with functional assessments before and after each period. Each participant serves as their own comparison: researchers will compare a period with standard care only (control phase) to a period with music therapy plus standard care (intervention phase), the order of which will be randomized in advance.

Detailed description: Rationale: Stroke is a highly disabling condition, for which music therapy is regularly used in rehabilitation. Motivation is considered to be a mechanism for functional improvements, including in neurologic music therapy (NMT), likely due to potential mood improvements, but it is not generally explicitly investigated. This motivation level may in turn affect not only functional outcomes and subjective well-being, but also adherence to other rehabilitation therapies.

Objectives: The primary goal of the study is to investigate motivation as an underlying mechanism of neurologic music therapy (NMT) for stroke patients experiencing upper-limb impairments and/or cognitive deficits, in the sub-acute phase of stroke. A secondary goal is to assess NMT-related changes in motor function, cognitive outcomes, and self-reported measures of well-being.

The hypothesis is that NMT will increase motivation, and that increased motivational state will positively affect functioning in both motor and/or cognitive domains.

Study design: The study has a longitudinal, single-subject design; as stroke patients are not a homogenous group, this design is adopted to control for expected within-subject variations. To account for variability in brain damage that is caused by stroke, each subject thus serves as their own control, and a longitudinal, repeated-measures design is selected. Participants will be randomized into two groups for a cross-over design, either receiving the intervention or the control phase first or vice versa, which counters order effects and assesses intervention effectiveness (as part of the secondary goals).

All subjects will receive NMT targeting both upper- limb movement and attention. All participants will receive a target of 9 NMT sessions (participants who complete a minimum of 6 sessions will be included in the analysis) over 3-6 weeks (depending on the rehabilitation trajectory, as subacute patients generally are admitted for a minimum of ± 6 and a maximum of 16 weeks), aiming for an average of 3 sessions per week, but adjusted to a patient's expected length of stay and ability, using a tailored approach.

Participants will receive three measurements. A baseline measure (TP1), on the first week of the rehabilitation trajectory, a second measure (TP2) either after the treatment/intervention period or control/ care as usual period (depending on the randomisation) and a post-treatment (TP3). The time interval between TP1- TP2 and TP2-TP3 are at least 21 days (3 weeks), with a margin of maximum 4-7 days, depending on their expected length of stay in the care facility.

Study population: In order to be eligible to participate in the study, a participant should be above 18 years of age and have had their first-ever supratentorial stroke between 2 weeks and up to 6 months before enrollment. Moreover, participants will have a referral for a paretic upper limb, i.e., partial loss of the capacity to carry out a voluntary upper limb movement and/or difficulty with attention/concentration, (e.g., complaints of being easily distractible, or unable to focus on a specific task in the presence of competing information, or complain of decline in attention). Participants must be able to receive music therapy for a minimum of 2-3 sessions per week, aiming for a total of 9 sessions over a minimum of three weeks, reducing this to 6 sessions in 2 weeks if required. The frequency of sessions is based on their ability and expected length of stay. Good command of the Dutch or English language is also a prerequisite for participation.

Participants will be excluded if this is not their first stroke or if a second stroke occurs during their stay. Further exclusion criteria are the following: i) upper limb paralysis as assessed by a score \< 2 points on the Medical Research Scale (MRC) for muscle strength; ii) severe behavioural and/or cognitive problems preventing understanding or carrying out instructions or risk of dementia (a score \<21 on the Mini-mental state examination; MMSE); iii) severe communication problems, e.g., severe aphasia and/or apraxia of speech; iv) known psychiatric, substance abuse, or neurological comorbidity. For participants who score \<24 on the MMSE, a follow-up check will be carried out for a possible dementia diagnosis which would retrospectively lead to exclusion.

Sample size: In a previous study, 40 stroke patients in the sub-acute phase were allocated to either twenty 30-minute sessions of music-supported therapy (N = 20; 4 withdrew/excluded; 16 in final analysis) or twenty additional sessions of conventional therapy (N = 20; 2 withdrew/excluded; 18 in final analysis). The study found a significant correlation (r = .562, p = .024) between patients' intrinsic motivation to engage in musical activities as measured by the BMRQ at baseline and improvement of upper-limb function as measured by the Action Research Arm Test (ARAT) at 3 months, which was not found in the comparator of occupational/physical therapy (r = -.305, p \< .21), with a significant difference between correlations (z = 2.4, p \< .05). Using G power 3 analysis, the investigators estimated that 18 participants are needed to observe a similar effect size for a sufficiently powered study (α=0.05 and (1-β)=0.8; ρ H1 = 0.56). This indicates that 20 participants completing the entire protocol would be required to observe an effect of motivation in music therapy, with an expected attrition/missing data rate of 10-20%. This sample size is similar to the number of participants used in studies showing an effect for our secondary objectives, ranging from 14-20 participants, on the effects of music therapy on motor function, cognition, and psychological wellbeing. Recruitment will continue until 20 participants have completed the protocol.

Intervention: The intervention condition will consist of a target of up to 9 sessions in total, administered over an average of 5 weeks, but may span from 2 to 8 weeks according to the patient's length of stay at the Leo Polak Stroke Rehabilitation Centre. All music therapy interventions will be delivered by a registered music therapist. The protocol aims for participants to receive a minimum of two sessions per week over the duration of the study enrollment. However, this schedule may not be possible in every case due to the participants' length of stay. Participants who complete a minimum of 6 sessions will be included in the final analyses. The number of sessions each participant receives will be recorded and treated as a variable systematically recorded, and the number of sessions will be accounted for in the statistical analysis.

Main parameters/ endpoints: The main parameters of the study focus on the differences in motivation levels of participants as the result of applying NMT techniques in the subacute phase of stroke, comparing within-subject differences between changes related to the intervention and the control period. The motivation level of participants will be measured using the BMQ-S \[patient-rated\] as state-level motivation. The secondary parameters relate to behavioural outcomes of upper limb, and cognitive functions, as well as self-reported measures of well-being following NMT for within-participant comparisons between the intervention and control period.

Eligibility criteria: Inclusion Criteria:

* Subjects had their first-ever supratentorial stroke between 2 weeks and up to 6 months before enrolment
* Paretic upper limb and/or attention/ concentration problems
* Ability to communicate in Dutch or English

Exclusion Criteria:

* Severe (global) aphasia
* paralysis of upper limb
* severe cognitive decline (MMSE \<24)

Primary outcomes:
measure: Motivation: Brain Injury Rehabilitation Trust Motivation Questionnaire (BMQ-S) [self-reported]
timeFrame: This outcome measure will be administered at 3 different time points (TP): Baseline/TP1 (week1), Mid-Trial/TP2 (week 4) and Final Measures/TP3 (week 7).
Secondary outcomes:
measure: Motor Function: Action Research Arm Test (ARAT)
timeFrame: This outcome measure will be administered at 3 different time points (TP): Baseline/TP1 (week1), Mid-Trial/TP2 (week 4) and Final Measures/TP3 (week 7).
measure: Motor Function: Barthel Index (BI)
timeFrame: This outcome measure will be administered at 3 different time points (TP): Baseline/TP1 (week1), Mid-Trial/TP2 (week 4) and Final Measures/TP3 (week 7).
measure: Cognition: Cancellation Wechsler Adult Intelligence Scale (WAIS-IV)
timeFrame: This outcome measure will be administered at 3 different time points (TP): Baseline/TP1 (week1), Mid-Trial/TP2 (week 4) and Final Measures/TP3 (week 7).
measure: Cognition: Color-Word Interference Test, also known as Stroop test
timeFrame: This outcome measure will be administered at 3 different time points (TP): Baseline/TP1 (week1), Mid-Trial/TP2 (week 4) and Final Measures/TP3 (week 7).
measure: Cognition: WAIS IV Digit Span Test - Forward and Backward
timeFrame: This outcome measure will be administered at 3 different time points (TP): Baseline/TP1 (week1), Mid-Trial/TP2 (week 4) and Final Measures/TP3 (week 7).
measure: Cognition: Verbal Fluency Test
timeFrame: This outcome measure will be administered at 3 different time points (TP): Baseline/TP1 (week1), Mid-Trial/TP2 (week 4) and Final Measures/TP3 (week 7).
measure: Cognition: Trail Making Test (TMT)
timeFrame: This outcome measure will be administered at 3 different time points (TP): Baseline/TP1 (week1), Mid-Trial/TP2 (week 4) and Final Measures/TP3 (week 7).
Other outcomes:
measure: Motivation to engage in musical activities: Barcelona Music Reward Questionnaire (BMRQ)
timeFrame: This outcome measure will be administered once, during the baseline Test Point (TP1) (week 1).
measure: Quality of Life: EuroQol-5 (EQ-5D-5L)
timeFrame: This outcome measure will be administered at 3 different time points (TP): Baseline/TP1 (week1), Mid-Trial/TP2 (week 4) and Final Measures/TP3 (week 7).
measure: Mood: Depression Anxiety Stress Scale-21 (DASS-21)
timeFrame: This outcome measure will be administered at 3 different time points (TP): Baseline/TP1 (week1), Mid-Trial/TP2 (week 4) and Final Measures/TP3 (week 7).
measure: Mood: Visual Analogue Mood Scale (VAMS)
timeFrame: Within 10 minutes before the start of each music therapy session (pre intervention) and immediately after each music therapy session (post intervention).
measure: Personality Traits: The Big Five Index-Extra Short Form (BFI-2-XS)
timeFrame: This outcome measure will be administered once, during the baseline Test Point (TP1) (week 1).
measure: Optimism: Life Orientation Test- Revised (LOT-R)
timeFrame: This outcome measure will be administered once, during the baseline Test Point (TP1) (week 1).
measure: Brief self-report of therapy expectations and satisfaction with treatment
timeFrame: This outcome measure will be administered at 3 different time points (TP): Baseline/TP1 (week1), Mid-Trial/TP2 (week 4) and Final Measures/TP3 (week 7).
Locations:
city: Amsterdam
country: Netherlands
facility: Leo Polak Rehabilitation centre
state: Nederland
Study officials:
affiliation: Leiden University
name: Hanneke Hulst, PhD
role: STUDY_CHAIR
References:
citation: Altenmuller E, Marco-Pallares J, Munte TF, Schneider S. Neural reorganization underlies improvement in stroke-induced motor dysfunction by music-supported therapy. Ann N Y Acad Sci. 2009 Jul;1169:395-405. doi: 10.1111/j.1749-6632.2009.04580.x.
citation: Baltazar, M., Västfjäll, D., Asutay, E., Koppel, L., & Saarikallio, S. (2019). Is it me or the music? Stress reduction and the role of regulation strategies and music. Music & Science, 2. https://doi.org/10.1177/2059204319844161
citation: Barker-Collo SL, Feigin VL, Lawes CM, Parag V, Senior H, Rodgers A. Reducing attention deficits after stroke using attention process training: a randomized controlled trial. Stroke. 2009 Oct;40(10):3293-8. doi: 10.1161/STROKEAHA.109.558239. Epub 2009 Jul 23.
citation: Burger B, Thompson MR, Luck G, Saarikallio S, Toiviainen P. Influences of rhythm- and timbre-related musical features on characteristics of music-induced movement. Front Psychol. 2013 Apr 12;4:183. doi: 10.3389/fpsyg.2013.00183. eCollection 2013.
citation: Dimitriadis T, Della Porta D, Perschl J, Evers AWM, Magee WL, Schaefer RS. Motivation and music interventions in adults: A systematic review. Neuropsychol Rehabil. 2024 Jun;34(5):649-678. doi: 10.1080/09602011.2023.2224033. Epub 2023 Jun 21.
citation: Dwan T, Ownsworth T. The Big Five personality factors and psychological well-being following stroke: a systematic review. Disabil Rehabil. 2019 May;41(10):1119-1130. doi: 10.1080/09638288.2017.1419382. Epub 2017 Dec 22.
citation: Fine, E. & Delis, D. (2011) Delis-Kaplan Executive Functioning System. In J. S. Kreutzer, J. DeLuca, and B. Caplan (Eds) Encyclopedia of Clinical Neuropsychology,. New York, NY: Springer, pp. 796-801. doi: 10.1007/978-0-387-79948- 3_1539.
citation: Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98. doi: 10.1016/0022-3956(75)90026-6. No abstract available.
citation: Fujioka T, Dawson DR, Wright R, Honjo K, Chen JL, Chen JJ, Black SE, Stuss DT, Ross B. The effects of music-supported therapy on motor, cognitive, and psychosocial functions in chronic stroke. Ann N Y Acad Sci. 2018 May 24. doi: 10.1111/nyas.13706. Online ahead of print.
citation: Grau-Sanchez J, Duarte E, Ramos-Escobar N, Sierpowska J, Rueda N, Redon S, Veciana de Las Heras M, Pedro J, Sarkamo T, Rodriguez-Fornells A. Music-supported therapy in the rehabilitation of subacute stroke patients: a randomized controlled trial. Ann N Y Acad Sci. 2018 Apr 1. doi: 10.1111/nyas.13590. Online ahead of print.
citation: Grau-Sanchez J, Munte TF, Altenmuller E, Duarte E, Rodriguez-Fornells A. Potential benefits of music playing in stroke upper limb motor rehabilitation. Neurosci Biobehav Rev. 2020 May;112:585-599. doi: 10.1016/j.neubiorev.2020.02.027. Epub 2020 Feb 21.
citation: Kim SY, Kim JM, Stewart R, Kang HJ, Kim SW, Shin IS, Park MS, Cho KH, Yoon JS. Influences of personality traits on quality of life after stroke. Eur Neurol. 2013;69(3):185-92. doi: 10.1159/000345699. Epub 2013 Jan 10.
citation: Kwakkel G, Kollen BJ, van der Grond J, Prevo AJ. Probability of regaining dexterity in the flaccid upper limb: impact of severity of paresis and time since onset in acute stroke. Stroke. 2003 Sep;34(9):2181-6. doi: 10.1161/01.STR.0000087172.16305.CD. Epub 2003 Aug 7.
citation: Mas-Herrero, E., Marco-Pallares, J., Lorenzo-Seva, U., Zatorre, R. J., & Rodriguez-Fornells, A. (2012). Individual differences in music reward experiences. Music Perception: An Interdisciplinary Journal, 31(2), 118-138.
citation: Oddy M, Cattran C, Wood R. The development of a measure of motivational changes following acquired brain injury. J Clin Exp Neuropsychol. 2008 Jul;30(5):568-75. doi: 10.1080/13803390701555598.
citation: Olgiati E, Russell C, Soto D, Malhotra P. Motivation and attention following hemispheric stroke. Prog Brain Res. 2016;229:343-366. doi: 10.1016/bs.pbr.2016.06.011. Epub 2016 Sep 16.
citation: Oyake K, Suzuki M, Otaka Y, Tanaka S. Motivational Strategies for Stroke Rehabilitation: A Descriptive Cross-Sectional Study. Front Neurol. 2020 Jun 10;11:553. doi: 10.3389/fneur.2020.00553. eCollection 2020.
citation: Raglio A, Zaliani A, Baiardi P, Bossi D, Sguazzin C, Capodaglio E, Imbriani C, Gontero G, Imbriani M. Active music therapy approach for stroke patients in the post-acute rehabilitation. Neurol Sci. 2017 May;38(5):893-897. doi: 10.1007/s10072-017-2827-7. Epub 2017 Jan 30.
citation: Ripolles P, Rojo N, Grau-Sanchez J, Amengual JL, Camara E, Marco-Pallares J, Juncadella M, Vaquero L, Rubio F, Duarte E, Garrido C, Altenmuller E, Munte TF, Rodriguez-Fornells A. Music supported therapy promotes motor plasticity in individuals with chronic stroke. Brain Imaging Behav. 2016 Dec;10(4):1289-1307. doi: 10.1007/s11682-015-9498-x.
citation: Schaefer RS. Auditory rhythmic cueing in movement rehabilitation: findings and possible mechanisms. Philos Trans R Soc Lond B Biol Sci. 2014 Dec 19;369(1658):20130402. doi: 10.1098/rstb.2013.0402.
citation: Schneider S, Schonle PW, Altenmuller E, Munte TF. Using musical instruments to improve motor skill recovery following a stroke. J Neurol. 2007 Oct;254(10):1339-46. doi: 10.1007/s00415-006-0523-2. Epub 2007 Jan 27.
citation: Stone SP, Ali B, Auberleek I, Thompsell A, Young A. The Barthel index in clinical practice: use on a rehabilitation ward for elderly people. J R Coll Physicians Lond. 1994 Sep-Oct;28(5):419-23.
citation: Street AJ, Magee WL, Odell-Miller H, Bateman A, Fachner JC. Home-based neurologic music therapy for upper limb rehabilitation with stroke patients at community rehabilitation stage-a feasibility study protocol. Front Hum Neurosci. 2015 Sep 23;9:480. doi: 10.3389/fnhum.2015.00480. eCollection 2015.
citation: Street, A., Fachner, J. & Magee, W. (2019) Upper limb rehabilitation in chronic stroke using neurologic music therapy: Two contrasting case studies to inform on treatment delivery and patient suitability, Nordic Journal of Music Therapy, 28:5, 382-404, DOI: 10.1080/08098131.2019.1606848
citation: Thaut, M. H., & Hoemberg, V. (Eds.). (2014). Handbook of neurologic music therapy. Oxford University Press.
citation: Tong Y, Forreider B, Sun X, Geng X, Zhang W, Du H, Zhang T, Ding Y. Music-supported therapy (MST) in improving post-stroke patients' upper-limb motor function: a randomised controlled pilot study. Neurol Res. 2015 May;37(5):434-40. doi: 10.1179/1743132815Y.0000000034. Epub 2015 Apr 27.
citation: Verrienti G, Raccagni C, Lombardozzi G, De Bartolo D, Iosa M. Motivation as a Measurable Outcome in Stroke Rehabilitation: A Systematic Review of the Literature. Int J Environ Res Public Health. 2023 Feb 26;20(5):4187. doi: 10.3390/ijerph20054187.
citation: van Alphen R, Stams GJJM, Hakvoort L. Musical Attention Control Training for Psychotic Psychiatric Patients: An Experimental Pilot Study in a Forensic Psychiatric Hospital. Front Neurosci. 2019 Jun 7;13:570. doi: 10.3389/fnins.2019.00570. eCollection 2019.