Skip to main content

Parkinson’s Disease

  • Protocol
  • First Online:
Clinical Trials in Neurology

Part of the book series: Neuromethods ((NM,volume 138))

Abstract

Parkinson’s disease (PD) is recognized as one of the most common neurologic disorders, with an imperative need for research and new therapeutic interventions. Considering these characteristics, the aim of this book chapter is to analyze the 100 most cited clinical trials in PD, thus outlining methodological aspects, limitations, and challenges involved in this field. A systematic search of the literature between 2010 and 2015 was performed using the electronic database Web of Science. The main findings are reported and discussed as to contribute to the advance of clinical research in this area.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Notes

  1. 1.

    Access to Web of Science was provided by Countway Library—Harvard Medical School.

  2. 2.

    Some chapters in this book used an extended search for 10 years.

  3. 3.

    Little, R (2014) The Prevention and Treatment of Missing Data in Clinical Trials. N ENGL MED 367;14.

References

  1. Schapira AH, Jenner P (2011) Etiology and pathogenesis of Parkinson’s disease. Mov Disord 26:1049–1055. https://doi.org/10.1002/mds.23732

    Article  PubMed  Google Scholar 

  2. de Lau LML, Breteler MMB (2006) Epidemiology of Parkinson’s disease. Lancet Neurol 5:525–535. https://doi.org/10.1016/S1474-4422(06)70471-9

    Article  PubMed  Google Scholar 

  3. EMA (2012) Guideline on clinical investigation of medicinal products in the treatment of Parkinson’ s disease, vol 44. EMA, London, pp 1–16

    Google Scholar 

  4. Kowal SL, Dall TM, Chakrabarti R et al (2013) The current and projected economic burden of Parkinson’s disease in the United States. Mov Disord 28:311–318. https://doi.org/10.1002/mds.25292

    Article  PubMed  Google Scholar 

  5. Jankovic J, Disease P, Clinic D et al (2015) The future of research in Parkinson disease. JAMA Neurol 71:2014–2015. https://doi.org/10.1001/jamaneurol.2014.1717.Conflict

    Article  Google Scholar 

  6. Hauser RA, Hsu A, Kell S et al (2013) Extended-release carbidopa-levodopa (IPX066) compared with immediate-release carbidopa-levodopa in patients with Parkinson’s disease and motor fluctuations: a phase 3 randomised, double-blind trial. Lancet Neurol 12:346–356. https://doi.org/10.1016/S1474-4422(13)70025-5

    Article  PubMed  CAS  Google Scholar 

  7. Olanow CW, Kieburtz K, Odin P et al (2014) Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson’s disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol 13:141–149. https://doi.org/10.1016/S1474-4422(13)70293-X

    Article  PubMed  CAS  Google Scholar 

  8. Sawada H, Oeda T, Kuno S et al (2010) Amantadine for dyskinesias in parkinson’s disease: a randomized controlled trial. PLoS One 5:6–12. https://doi.org/10.1371/journal.pone.0015298

    Article  CAS  Google Scholar 

  9. Elm JJ, Goetz CG, Ravina B et al (2005) A responsive outcome for Parkinson’s disease neuroprotection futility studies. Ann Neurol 57:197–203. https://doi.org/10.1002/ana.20361

    Article  PubMed  Google Scholar 

  10. Collins LM, Murphy SA, Strecher V (2007) The multiphase optimization strategy (MOST) and the sequential multiple assignment randomized trial (SMART): new methods for more potent eHealth interventions. Am J Prev Med 32:S112–S118. https://doi.org/10.1016/j.amepre.2007.01.022

    Article  PubMed  PubMed Central  Google Scholar 

  11. Simuni T, Borushko E, Avram MJ et al (2010) Tolerability of isradipine in early Parkinson’s disease: a pilot dose escalation study. Mov Disord 25:2863–2866. https://doi.org/10.1002/mds.23308

    Article  PubMed  Google Scholar 

  12. Schapira AH, Stocchi F, Borgohain R et al (2013) Long-term efficacy and safety of safinamide as add-on therapy in early Parkinson’s disease. Eur J Neurol 20:271–280. https://doi.org/10.1111/j.1468-1331.2012.03840.x

    Article  PubMed  CAS  Google Scholar 

  13. Kieburtz K, Tilley BC, Elm JJ et al (2015) Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial. JAMA 313:584–593. https://doi.org/10.1001/jama.2015.120

    Article  PubMed  CAS  Google Scholar 

  14. Athauda D, Foltynie T (2014) The ongoing pursuit of neuroprotective therapies in Parkinson disease. Nat Rev Neurol 11:25–40. https://doi.org/10.1038/nrneurol.2014.226

    Article  PubMed  CAS  Google Scholar 

  15. D’Agostino RB (2009) The delayed-start study design. N Engl J Med 361:1304–1306. https://doi.org/10.1056/NEJMsm0904209

    Article  PubMed  Google Scholar 

  16. Barker RA, Stacy M, Brundin P (2013) A new approach to disease-modifying drug trials in Parkinson’s disease. J Clin Invest 123:2364–2365. https://doi.org/10.1172/JCI69690.2364

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Devos D, Moreau C, Devedjian JC et al (2014) Targeting chelatable iron as a therapeutic modality in Parkinson’s disease. Antioxid Redox Signal 21:195–210. https://doi.org/10.1089/ars.2013.5593

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Dorsey ER, Venuto C, Venkataraman V et al (2015) Novel methods and technologies for 21st-century clinical trials: a review. JAMA Neurol 72:582–588. https://doi.org/10.1001/jamaneurol.2014.4524

    Article  PubMed  PubMed Central  Google Scholar 

  19. Palfi S, Gurruchaga JM, Ralph GS et al (2014) Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson’s disease: a dose escalation, open-label, phase 1/2 trial. Lancet 383:1138–1146. https://doi.org/10.1016/S0140-6736(13)61939-X

    Article  PubMed  CAS  Google Scholar 

  20. Williams HC, Burden-Teh E, Nunn AJ (2015) What is a pragmatic clinical trial? J Invest Dermatol 135:e33. https://doi.org/10.1038/jid.2015.134

    Article  CAS  Google Scholar 

  21. Munneke M, Nijkrake MJ, Keus SH et al (2010) Efficacy of community-based physiotherapy networks for patients with Parkinson’s disease: a cluster-randomised trial. Lancet Neurol 9:46–54. https://doi.org/10.1016/S1474-4422(09)70327-8

    Article  PubMed  Google Scholar 

  22. Goodwin VA, Richards SH, Henley W et al (2011) An exercise intervention to prevent falls in people with Parkinson’s disease: a pragmatic randomised controlled trial. J Neurol Neurosurg Psychiatry 82:1232–1238. https://doi.org/10.1136/jnnp-2011-300919

    Article  PubMed  Google Scholar 

  23. Bloem BR, Munneke M (2014) Revolutionising management of chronic disease: the ParkinsonNet approach. BMJ 348:g1838–g1838. https://doi.org/10.1136/bmj.g1838

    Article  PubMed  Google Scholar 

  24. Schrag A, Sauerbier A, Chaudhuri KR (2015) New clinical trials for nonmotor manifestations of Parkinson’s disease. Mov Disord 30:1490–1503. https://doi.org/10.1002/mds.26415

    Article  PubMed  CAS  Google Scholar 

  25. Martinez-Ramirez D, Hu W, Bona AR et al (2015) Update on deep brain stimulation in Parkinson’s disease. Transl Neurodegener 4:12. https://doi.org/10.1186/s40035-015-0034-0

    Article  PubMed  PubMed Central  Google Scholar 

  26. Deuschl G, Schüpbach M, Knudsen K et al (2013) Stimulation of the subthalamic nucleus at an earlier disease stage of Parkinson’s disease: concept and standards of the EARLYSTIM-study. Parkinsonism Relat Disord 19:56–61. https://doi.org/10.1016/j.parkreldis.2012.07.004

    Article  PubMed  Google Scholar 

  27. Witt K, Granert O, Daniels C et al (2013) Relation of lead trajectory and electrode position to neuropsychological outcomes of subthalamic neurostimulation in Parkinson’s disease: results from a randomized trial. Brain 136:2109–2119. https://doi.org/10.1093/brain/awt151

    Article  PubMed  Google Scholar 

  28. Daniels C, Krack P, Volkmann J et al (2010) Risk factors for executive dysfunction after subthalamic nucleus stimulation in Parkinson’s disease. Mov Disord 25:1583–1589. https://doi.org/10.1002/mds.23078

    Article  PubMed  Google Scholar 

  29. Vivas J, Arias P, Cudeiro J (2011) Aquatic therapy versus conventional land-based therapy for Parkinson’s disease: an open-label pilot study. Arch Phys Med Rehabil 92:1202–1210. https://doi.org/10.1016/j.apmr.2011.03.017

    Article  PubMed  Google Scholar 

  30. Earhart GM, Duncan RP, Huang JL et al (2015) Comparing interventions and exploring neural mechanisms of exercise in Parkinson disease: a study protocol for a randomized controlled trial. BMC Neurol 15:9. https://doi.org/10.1186/s12883-015-0261-0

    Article  PubMed  PubMed Central  Google Scholar 

  31. Goodwin VA, Richards SH, Taylor RS et al (2008) The effectiveness of exercise interventions for people with Parkinson’s disease: a systematic review and meta-analysis. Mov Disord 23:631–640. https://doi.org/10.1002/mds.21922

    Article  PubMed  Google Scholar 

  32. Trenkwalder C, Kies B, Rudzinska M et al (2011) Rotigotine effects on early morning motor function and sleep in Parkinson’s disease: a double-blind, randomized, placebo-controlled study (RECOVER). Mov Disord 26:90–99. https://doi.org/10.1002/mds.23441

    Article  PubMed  Google Scholar 

  33. Watts RL, Lyons KE, Pahwa R et al (2010) Onset of dyskinesia with adjunct ropinirole prolonged-release or additional levodopa in early Parkinson’s disease. Mov Disord 25:858–866. https://doi.org/10.1002/mds.22890

    Article  PubMed  Google Scholar 

  34. Goetz CG, Tilley BC, Shaftman SR et al (2008) Movement disorder society-sponsored revision of the unified Parkinson’s disease rating scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 23:2129–2170. https://doi.org/10.1002/mds.22340

    Article  PubMed  Google Scholar 

  35. Schapira AH, McDermott MP, Barone P et al (2013) Pramipexole in patients with early Parkinson’s disease (PROUD): a randomised delayed-start trial. Lancet Neurol 12:747–755. https://doi.org/10.1016/S1474-4422(13)70117-0

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Eggers C, Fink GR, Nowak DA (2010) Theta burst stimulation over the primary motor cortex does not induce cortical plasticity in Parkinson’s disease. J Neurol 257:1669–1674. https://doi.org/10.1007/s00415-010-5597-1

    Article  PubMed  Google Scholar 

  37. Van Der Brug MP, Singleton A, Gasser T, Lewis PA (2015) Parkinson’s disease: from human genetics to clinical trials. Sci Transl Med 7(305):205ps20

    PubMed  PubMed Central  Google Scholar 

  38. Bartus RT, Weinberg MS, Samulski RJ (2014) Parkinson’s disease gene therapy: success by design meets failure by efficacy. Mol Ther 22:487–497. https://doi.org/10.1038/mt.2013.281

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Lewis JA (1999) Statistical principles for clinical trials (ICH E9): an introductory note on an international guideline. Stat Med 18:1903–1904. https://doi.org/10.1002/(SICI)1097-0258(19990815)18:15<1903::AID-SIM188>3.0.CO;2-F

    Article  PubMed  CAS  Google Scholar 

  40. Dmitrienko A, Tamhane AC, Wang X, Chen X (2006) Stepwise gatekeeping procedures in clinical trial applications. Biom J 48:984–991. https://doi.org/10.1002/bimj.200610274

    Article  PubMed  Google Scholar 

  41. Benninger DH, Lomarev M, Lopez G et al (2010) Transcranial direct current stimulation for the treatment of Parkinson’s disease. J Neurol Neurosurg Psychiatry 81:1105–1111. https://doi.org/10.1136/jnnp.2009.202556

    Article  PubMed  PubMed Central  Google Scholar 

  42. Moreau C, Delval A, Defebvre L et al (2012) Methylphenidate for gait hypokinesia and freezing in patients with Parkinson’s disease undergoing subthalamic stimulation: a multicentre, parallel, randomised, placebo-controlled trial. Lancet Neurol 11:589–596. https://doi.org/10.1016/S1474-4422(12)70106-0

    Article  PubMed  CAS  Google Scholar 

  43. Factor S, Mark MH, Watts R et al (2010) A long-term study of istradefylline in subjects with fluctuating Parkinson’s disease. Parkinsonism Relat Disord 16:423–426. https://doi.org/10.1016/j.parkreldis.2010.02.014

    Article  PubMed  Google Scholar 

  44. Williams A, Gill S, Varma T et al (2010) Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson’s disease (PD SURG trial): a randomised, open-label trial. Lancet Neurol 9:581–591. https://doi.org/10.1016/S1474-4422(10)70093-4

    Article  PubMed  PubMed Central  Google Scholar 

  45. Marks WJ, Bartus RT, Siffert J et al (2010) Gene delivery of AAV2-neurturin for Parkinson’s disease: a double-blind, randomised, controlled trial. Lancet Neurol 9:1164–1172. https://doi.org/10.1016/S1474-4422(10)70254-4

    Article  PubMed  CAS  Google Scholar 

  46. Li F, Harmer P, Fitzgerald K et al (2012) Tai chi and postural stability in patients with Parkinson’s disease. N Engl J Med 366:511–519. https://doi.org/10.1056/NEJMoa1107911

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Schulz KF, Altman DG, Moher D, for the CONSORT Group (2010) CONSORT 2010 Statement: updated guidelines for reporting parallel group randomized trials. Open Med 4(1):60–68

    Google Scholar 

  48. Schulz KF, Grimes DA (2002) Epidemiology series Generation of allocation sequences in randomised trials: chance, not choice Epidemiology series Generation of allocation sequences in randomised trials: chance, not choice. Lancet 359:515–519

    Article  PubMed  Google Scholar 

  49. Müller T, Kuhn W (2009) Homocysteine levels after acute levodopa intake in patients with Parkinson’s disease. Mov Disord 24:1339–1343. https://doi.org/10.1002/mds.22607

    Article  PubMed  Google Scholar 

  50. Follett K, Weaver F, Stern M (2010) Pallidal versus subthalamic deep-brain stimulation for Parkinson’s disease. N Engl J Med 362:2077–2091

    Article  CAS  PubMed  Google Scholar 

  51. Schuepbach WMM, Rau J, Knudsen K et al (2013) Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med 368:610–622. https://doi.org/10.1056/NEJMoa1205158

    Article  PubMed  CAS  Google Scholar 

  52. Tickle-Degnen L, Ellis T, Saint-Hilaire MH et al (2010) Self-management rehabilitation and health-related quality of life in Parkinson’s disease: a randomized controlled trial. Mov Disord 25:194–204. https://doi.org/10.1002/mds.22940

    Article  PubMed  PubMed Central  Google Scholar 

  53. LeWitt PA, Rezai AR, Leehey MA et al (2011) AAV2-GAD gene therapy for advanced Parkinson’s disease: a double-blind, sham-surgery controlled, randomised trial. Lancet Neurol 10:309–319. https://doi.org/10.1016/S1474-4422(11)70039-4

    Article  PubMed  CAS  Google Scholar 

  54. Gupta SK (2011) Intention-to-treat concept: a review. Perspect Clin Res 2:109–112. https://doi.org/10.4103/2229-3485.83221

    Article  PubMed  PubMed Central  Google Scholar 

  55. Emre M, Tsolaki M, Bonuccelli U et al (2010) Memantine for patients with Parkinson’s disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 9:969–977

    Article  CAS  PubMed  Google Scholar 

  56. Shulman LM, Gruber-Baldini AL, Anderson KE et al (2010) The clinically important difference on the unified Parkinson’s disease rating scale. Arch Neurol 67:64–70. https://doi.org/10.1001/archneurol.2009.295

    Article  PubMed  Google Scholar 

  57. Shiner T, Seymour B, Wunderlich K et al (2012) Dopamine and performance in a reinforcement learning task: evidence from Parkinson’s disease. Brain 135:1871–1883. https://doi.org/10.1093/brain/aws083

    Article  PubMed  PubMed Central  Google Scholar 

  58. Little TD, Jorgensen TD, Lang KM, Moore EWG (2014) On the joys of missing data. J Pediatr Psychol 39:151–162. https://doi.org/10.1093/jpepsy/jst048

    Article  PubMed  Google Scholar 

  59. Goetz CG, Luo S, Wang L et al (2015) Handling missing values in the MDS-UPDRS. Mov Disord 00:1–7. https://doi.org/10.1002/mds.26153

    Article  Google Scholar 

  60. Wang R, Lagakos SW, Ware JH et al (2007) Statistics in medicine — reporting of subgroup analyses in clinical trials. N Engl J Med 357:2189–2194. https://doi.org/10.1056/NEJMsr077003

    Article  PubMed  CAS  Google Scholar 

  61. Pannucci CJ, Wilkins EG (2010) Identifying and avoiding bias in research. Plast Reconstr Surg 126:619–625. https://doi.org/10.1097/PRS.0b013e3181de24bc

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to acknowledge Cristina Russo, Aura Hurtado, Felipe Jones, Anthony O’Brien, Beatriz Costa, Isadora Ferreira, and Felipe Fregni for the manuscript review.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Felipe Fregni .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Villarreal, M.F., Huerta-Gutierrez, R., Fregni, F. (2018). Parkinson’s Disease. In: Fregni, F. (eds) Clinical Trials in Neurology. Neuromethods, vol 138. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7880-9_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-7880-9_5

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7879-3

  • Online ISBN: 978-1-4939-7880-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics