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BMC Neurology
Published in: BMC Neurology 1/2015

Open Access 01-12-2015 | Study protocol

The cyclical lower extremity exercise for Parkinson’s trial (CYCLE): methodology for a randomized controlled trial

Authors: Anson B Rosenfeldt, Matthew Rasanow, Amanda L Penko, Erik B Beall, Jay L Alberts

Published in: BMC Neurology | Issue 1/2015

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Abstract

Background

Motor and non-motor impairments affect quality of life in individuals with Parkinson’s disease. Our preliminary research indicates that forced exercise cycling, a mode of exercise in which a participant’s voluntary rate of exercise is augmented on a stationary cycle, results in global improvements in the cardinal symptoms of Parkinson’s disease. The objective of the Cyclical Lower Extremity Exercise (CYCLE) trial for Parkinson’s disease is to determine the effects of forced exercise cycling on motor and non-motor performance when compared to voluntary rate cycling and a non-exercise control group. Additionally, we plan to identify any associated changes in neural activity determined by functional magnetic resonance imaging.

Methods/Design

A total of 100 individuals with mild to moderate idiopathic Parkinson’s disease will participate in a single-center, parallel-group, rater-blind study. Participants will be randomized 2:2:1 into a forced exercise, voluntary exercise, or no-exercise control group, respectively. Both exercise groups will cycle 3 times per week for 8 weeks at identical aerobic intensities for 40 minutes, but participants in the forced exercise group will cycle 30% faster than their voluntary rate by means of an augmented motorized bicycle. Neuroimaging, clinical, and biomechanical assessments of motor and non-motor performance will be made at baseline both ‘on’ and ‘off’ medication, after four weeks of exercise (midpoint), end of treatment, 4 weeks after end of treatment, and 8 weeks after end of treatment.

Discussion

CYCLE trial will play a critical role in determining the effectiveness of two different types of aerobic exercise, forced and voluntary, on motor and non-motor performance in individuals with Parkinson’s disease. Additionally, the coupling of clinical, biomechanical, and neuroimaging outcomes has the potential to provide insight into mechanisms underlying change in function as a result of exercise.

Trial registration

Clinicaltrials.gov registration number NCT01636297.
Literature
1.
Dorsey ER, Constantinescu R, Thompson JP, Biglan KM, Holloway RG, Kieburtz K, et al. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology. 2007;68(5):384–6.CrossRefPubMed
2.
Kaltenboeck A, Johnson SJ, Davis MR, Birnbaum HG, Carroll CA, Tarrants ML, et al. Direct costs and survival of medicare beneficiaries with early and advanced Parkinson’s disease. Parkinsonism Relat Disord. 2012;18(4):321–6.CrossRefPubMed
3.
Aarsland D, Kurz MW. The epidemiology of dementia associated with Parkinson disease. J Neurol Sci. 2010;289(1-2):18–22.CrossRefPubMed
4.
Chaudhuri KR, Martinez-Martin P. Quantitation of non-motor symptoms in Parkinson’s disease. Eur J Neurol. 2008;15 Suppl 2:2–7.CrossRefPubMed
5.
Macht M, Schwarz R, Ellgring H. Patterns of psychological problems in Parkinson’s disease. Acta Neurol Scand. 2005;111(2):95–101.CrossRefPubMed
6.
Hirsch MA, Farley BG. Exercise and neuroplasticity in persons living with Parkinson’s disease. Eur J Phys Rehabil Med. 2009;45(2):215–29.PubMed
7.
Tsai CH, Lo SK, See LC, Chen HZ, Chen RS, Weng YH, et al. Environmental risk factors of young onset Parkinson’s disease: a case-control study. Clin Neurol Neurosurg. 2002;104(4):328–33.CrossRefPubMed
8.
Shu HF, Yang T, Yu SX, Huang HD, Jiang LL, Gu JW, et al. Aerobic exercise for Parkinson’s disease: a systematic review and meta-analysis of randomized controlled trials. PLoS One. 2014;9(7):e100503.CrossRefPubMedPubMedCentral
9.
Tomlinson CL, Herd CP, Clarke CE, Meek C, Patel S, Stowe R, et al. Physiotherapy for Parkinson’s disease: a comparison of techniques. Cochrane Database Syst Rev. 2014;6:CD002815.PubMed
10.
Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 2002;25(6):295–301.CrossRefPubMed
11.
Knaepen K, Goekint M, Heyman EM, Meeusen R. Neuroplasticity - exercise-induced response of peripheral brain-derived neurotrophic factor: a systematic review of experimental studies in human subjects. Sports Med. 2010;40(9):765–801.CrossRefPubMed
12.
Lau YS, Patki G, Das-Panja K, Le WD, Ahmad SO. Neuroprotective effects and mechanisms of exercise in a chronic mouse model of Parkinson’s disease with moderate neurodegeneration. Eur J Neurosci. 2011;33(7):1264–74.CrossRefPubMedPubMedCentral
13.
Zigmond MJ, Smeyne RJ. Exercise: is it a neuroprotective and if so, how does it work? Parkinsonism Relat Disord. 2014;20 Suppl 1:S123–7.CrossRefPubMed
14.
Petzinger GM, Fisher BE, McEwen S, Beeler JA, Walsh JP, Jakowec MW. Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson’s disease. Lancet Neurol. 2013;12(7):716–26.CrossRefPubMedPubMedCentral
15.
Murray DK, Sacheli MA, Eng JJ, Stoessl AJ. The effects of exercise on cognition in Parkinson’s disease: a systematic review. Transl Neurodegener. 2014;3(1):5.CrossRefPubMedPubMedCentral
16.
Ridgel AL, Peacock CA, Fickes EJ, Kim CH. Active-assisted cycling improves tremor and bradykinesia in Parkinson’s disease. Arch Phys Med Rehabil. 2012;93(11):2049–54.CrossRefPubMed
17.
Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends Neurosci. 1989;12(10):366–75.CrossRefPubMed
18.
Wichmann T, DeLong MR. Pathophysiology of parkinsonian motor abnormalities. Adv Neurol. 1993;60:53–61.PubMed
19.
Wichmann T, DeLong MR. Models of basal ganglia function and pathophysiology of movement disorders. Neurosurg Clin N Am. 1998;9(2):223–36.PubMed
20.
Ridgel AL, Vitek JL, Alberts JL. Forced, not voluntary, exercise improves motor function in Parkinson’s disease patients. Neurorehabil Neural Repair. 2009;23(6):600–8.CrossRefPubMed
21.
Alberts JL, Linder SM, Penko AL, Lowe MJ, Phillips M. It is not about the bike, it is about the pedaling: forced exercise and Parkinson’s disease. Exerc Sport Sci Rev. 2011;39(4):177–86.PubMed
22.
Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, et al. Movement disorder society-sponsored revision of the unified Parkinson’s disease rating scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008;23(15):2129–70.CrossRefPubMed
23.
Beall EB, Lowe MJ, Alberts JL, Frankemolle AM, Thota AK, Shah C, et al. The effect of forced-exercise therapy for Parkinson’s disease on motor cortex functional connectivity. Brain Connect. 2013;3(2):190–8.CrossRefPubMedPubMedCentral
24.
Qutubuddin A, Reis T, Alramadhani R, Cifu DX, Towne A, Carne W. Parkinson’s disease and forced exercise: a preliminary study. Rehabil Res Pract. 2013;2013:375267.PubMedPubMedCentral
25.
Shulman LM, Katzel LI, Ivey FM, Sorkin JD, Favors K, Anderson KE, et al. Randomized clinical trial of 3 types of physical exercise for patients with Parkinson disease. JAMA Neurol. 2013;70(2):183–90.CrossRefPubMedPubMedCentral
26.
Rascol OJ, Sabatini U, Chollet F, Montastruc JL, Marc-Vergnes JP, Rascol A. Impaired activity of the supplementary motor area in akinetic patients with Parkinson’s disease: improvement by the dopamine agonist apomorphine. Adv Neurol. 1993;60:419–21.PubMed
27.
Rascol O, Sabatini U, Chollet F, Celsis P, Montastruc JL, Marc-Vergnes JP, et al. Supplementary and primary sensory motor area activity in Parkinson’s disease: regional cerebral blood flow changes during finger movements and effects of apomorphine. Arch Neurol. 1992;49(2):144–8.CrossRefPubMed
28.
Kaminsky LA. ACSM’s resource manual for guidelines for exercise testing and prescription. 5th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2006.
29.
Karvonen MJ, Kentala E, Mustala O. The effects of training on heart rate; a longitudinal study. Ann Med Exp Biol Fenn. 1957;35(3):307–15.PubMed
30.
Morris S, Morris ME, Iansek R. Reliability of measurements obtained with the Timed “Up & Go” test in people with Parkinson disease. Phys Ther. 2001;81(2):810–8.PubMed
31.
Peto V, Jenkinson C, Fitzpatrick R. PDQ-39: a review of the development, validation and application of a Parkinson’s disease quality of life questionnaire and its associated measures. J Neurol. 1998;245 Suppl 1:S10–4.CrossRefPubMed
32.
Doty RL, Shaman P, Dann M. Development of the University of Pennsylvania smell identification test: a standardized microencapsulated test of olfactory function. Physiol Behav. 1984;32(3):489–502.CrossRefPubMed
33.
Hogervorst E, Combrinck M, Lapuerta P, Rue J, Swales K, Budge M. The Hopkins verbal learning test and screening for dementia. Dement Geriatr Cogn Disord. 2002;13(1):13–20.CrossRefPubMed
34.
Arnau RC, Meagher MW, Norris MP, Bramson R. Psychometric evaluation of the beck depression inventory-II with primary care medical patients. Health Psychol. 2001;20(2):112–9.CrossRefPubMed
35.
Thompson MD, Scott JG, Dickson SW, Schoenfeld JD, Ruwe WD, Adams RL. Clinical utility of the trail making test practice time. Clin Neuropsychol. 1999;13(4):450–5.CrossRefPubMed
36.
Fitts PM, Weinstein M, Rappaport M, Anderson N, Leonard JA. Stimulus correlates of visual pattern recognition: a probability approach. J Exp Psychol. 1956;51(1):1–11.CrossRefPubMed
37.
Alberts JL, SM L. The utilization of biomechanics to understand and manage the acute and long-term effects of concussion. Kines Rev. 2015. In Press.
38.
Hinton-Bayre A, Geffen G. Comparability, reliability, and practice effects on alternate forms of the digit symbol substitution and symbol digit modalities tests. Psychol Assess. 2005;17(2):237–41.CrossRefPubMed
39.
Rudick RA, Miller D, Bethoux F, Rao SM, Lee JC, Stough D, et al. The Multiple Sclerosis Performance Test (MSPT): an iPad-based disability assessment tool. J Vis Exp. 2014;88:e51318.PubMed
40.
Ozinga SJ, Alberts JL. Quantification of postural stability in older adults using mobile technology. Exp Brain Res. 2014;232(12):3861–72.CrossRefPubMed
41.
Alberts JL, Hirsch JR, Koop MM, Schindler DD, Kana DE, Linder SM, et al. Using accelerometer and gyroscopic measures to quantify postural stability. J Athletic Training. Epub Apr 6 2015.
42.
Alberts JL, Hirsch JR, Koop MM, Schindler DD, Burke D, Dey T, et al. Quantification of the balance error scoring system with portable technology. Med Sci Sport Exerc. 2015. In Review.
43.
Ozinga S, Machado AG, Koop MM, Rosenfeldt AB, Alberts, JL. Objective assessment of postural stability in Parkinson’s disease using mobile technology. Mov Disord. Epub Mar 25 2015
44.
Wang YC, Magasi SR, Bohannon RW, Reuben DB, McCreath HE, Bubela DJ, et al. Assessing dexterity function: a comparison of two alternatives for the NIH Toolbox. J Hand Ther. 2011;24(4):313–20. quiz 321.CrossRefPubMedPubMedCentral
45.
Cox RW, Hyde JS. Software tools for analysis and visualization of fMRI data. NMR Biomed. 1997;10(4-5):171–8.CrossRefPubMed
46.
Beall EB, Lowe MJ. SimPACE: generating simulated motion corrupted BOLD data with synthetic-navigated acquisition for the development and evaluation of SLOMOCO: a new, highly effective slicewise motion correction. Neuroimage. 2014;101:21–34.CrossRefPubMedPubMedCentral
47.
Beall EB, Lowe MJ. Isolating physiologic noise sources with independently determined spatial measures. Neuroimage. 2007;37(4):1286–300.CrossRefPubMed
48.
Lowe MJ, Sorenson JA. Spatially filtering functional magnetic resonance imaging data. Magn Reson Med. 1997;37(5):723–9.CrossRefPubMed
49.
Lowe MJ, Russell DP. Treatment of baseline drifts in fMRI time series analysis. J Comput Assist Tomogr. 1999;23(3):463–73.CrossRefPubMed
50.
Luh WM, Wong EC, Bandettini PA, Hyde JS. QUIPSS II with thin-slice TI1 periodic saturation: a method for improving accuracy of quantitative perfusion imaging using pulsed arterial spin labeling. Magn Reson Med. 1999;41(6):1246–54.CrossRefPubMed
Metadata
Title
The cyclical lower extremity exercise for Parkinson’s trial (CYCLE): methodology for a randomized controlled trial
Authors
Anson B Rosenfeldt
Matthew Rasanow
Amanda L Penko
Erik B Beall
Jay L Alberts
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2015
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-015-0313-5

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