TAME-PD - Physical Therapy, Atomoxetine and, Methylphenidate, to Enhance Gait and Balance in Parkinson's Disease

NCT02879136 | Completed Early Phase 1

• 1 other identifier: 16-277
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Gait and balance problems are a significant source of disability in patients with Parkinson disease. Physical therapy remains one of the main treatments. On the other hand some medications, such as methyphenidate and atomoxetine, have been tried with promising results. The outcomes in gait and balance in Parkinson disease after a combination of physical therapy and the medications mentioned above have not been explored yet. The investigators want to evaluate whether the addition of medication, either low dose of methylphenidate or atomoxetine, to physical therapy will achieve improvement in gait and balance in Parkinson disease more than physical therapy alone. The investigators propose a pilot, single center, rater blind, prospective randomized trial. 2-arm-parallel group, intention-to-treat analysis.

Conditions

Parkinson's Disease, Idiopathic

Keywords

Gait; Balance; PD

Outcome Measures

Primary Outcomes (1)

• Balance Evaluation

  Change in the balance evaluation systems test, MiniBest is standard gait analysis measure conducted by physical therapists.

  12 weeks

Secondary Outcomes (1)

• Change in gait

  12 weeks

Other Outcomes (1)

• Motor function

  12 weeks

Study Arms (3)

Physical Therapy

ACTIVE COMPARATOR

Physical Therapy (PT) will consist of two weekly sessions over a 12 week period using the Mellen center protocol PT for PD.

Other: Physical Therapy

Physical Therapy plus Methylphenidate

ACTIVE COMPARATOR

Methylphenidate 20 mg daily in combination with PT

Drug: Methylphenidate; Other: Physical Therapy

Physical Therapy plus Atomoxetine

ACTIVE COMPARATOR

Atomoxetine 10 mg daily in combination with PT or PT alone.

Other: Physical Therapy; Drug: Atomoxetine

Interventions

Atomoxetine DRUG

Patient will be randomized to Atomoxetine

Also known as: Straterra

Physical Therapy plus Atomoxetine

Methylphenidate DRUG

Patient will be randomized to Methylphenidate

Also known as: Ritalin

Physical Therapy plus Methylphenidate

Physical Therapy OTHER

All Patients will have standard of care PT used for PD patients

Also known as: PT

Physical Therapy; Physical Therapy plus Atomoxetine; Physical Therapy plus Methylphenidate

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with PD having significant balance or gait disorder with a score ≥2 in the Unified Parkinson Disease Rating Scale (UPDRS) 3.10 item 'independent walking but with substantial gait impairment; not related to off periods' occurring despite satisfactory motor control by dopaminergic therapy, with a medication regimen unlikely to change in the next 30 days.

You may not qualify if:

• Previous participation in PD-specific PT.
• Presence of signs and symptoms suggestive of atypical parkinsonism.
• Concomitant conditions that may affect significantly the evaluation of balance or gait, including orthopedic, rheumatologic or other neurological diseases.
• Contraindication for physical therapy
• Comorbidities that contraindicate the use of the methylphenidate or atomoxetine: history of substance abuse, current severe anxiety, depression or psychosis, epilepsy, hyperthyroidism, glaucoma, cardiac arrhythmia, history of Tourette syndrome, hepatic disease, allergy to methylphenidate or atomoxetine.
• Concurrent use of MAO inhibitors, or use in the last two weeks.
• Previous deep brain stimulation procedure.
• Punctuation of 5 in Hoehn and Yard modified scale: 'Wheelchair bound or bedridden unless aided'.

Sponsors & Collaborators

• Hubert Fernandez: lead

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Related Publications (18)

• Boonstra TA, van der Kooij H, Munneke M, Bloem BR. Gait disorders and balance disturbances in Parkinson's disease: clinical update and pathophysiology. Curr Opin Neurol. 2008 Aug;21(4):461-71. doi: 10.1097/WCO.0b013e328305bdaf.

  PMID: 18607208 BACKGROUND

• Williams DR, Watt HC, Lees AJ. Predictors of falls and fractures in bradykinetic rigid syndromes: a retrospective study. J Neurol Neurosurg Psychiatry. 2006 Apr;77(4):468-73. doi: 10.1136/jnnp.2005.074070.

  PMID: 16543524 BACKGROUND

• Moreau C, Cantiniaux S, Delval A, Defebvre L, Azulay JP. [Gait disorders in Parkinson's disease: and pathophysiological approaches]. Rev Neurol (Paris). 2010 Feb;166(2):158-67. doi: 10.1016/j.neurol.2009.05.010. Epub 2009 Jul 18. French.

  PMID: 19616816 BACKGROUND

• Wielinski CL, Erickson-Davis C, Wichmann R, Walde-Douglas M, Parashos SA. Falls and injuries resulting from falls among patients with Parkinson's disease and other parkinsonian syndromes. Mov Disord. 2005 Apr;20(4):410-415. doi: 10.1002/mds.20347.

  PMID: 15580552 BACKGROUND

• Collomb-Clerc A, Welter ML. Effects of deep brain stimulation on balance and gait in patients with Parkinson's disease: A systematic neurophysiological review. Neurophysiol Clin. 2015 Nov;45(4-5):371-88. doi: 10.1016/j.neucli.2015.07.001. Epub 2015 Aug 28.

  PMID: 26319759 BACKGROUND

• Nutt JG, Horak FB, Bloem BR. Milestones in gait, balance, and falling. Mov Disord. 2011 May;26(6):1166-74. doi: 10.1002/mds.23588.

  PMID: 21626560 BACKGROUND

• Auriel E, Hausdorff JM, Herman T, Simon ES, Giladi N. Effects of methylphenidate on cognitive function and gait in patients with Parkinson's disease: a pilot study. Clin Neuropharmacol. 2006 Jan-Feb;29(1):15-7. doi: 10.1097/00002826-200601000-00005.

  PMID: 16518128 BACKGROUND

• Pollak L, Dobronevsky Y, Prohorov T, Bahunker S, Rabey JM. Low dose methylphenidate improves freezing in advanced Parkinson's disease during off-state. J Neural Transm Suppl. 2007;(72):145-8. doi: 10.1007/978-3-211-73574-9_17.

  PMID: 17982887 BACKGROUND

• Devos D, Krystkowiak P, Clement F, Dujardin K, Cottencin O, Waucquier N, Ajebbar K, Thielemans B, Kroumova M, Duhamel A, Destee A, Bordet R, Defebvre L. Improvement of gait by chronic, high doses of methylphenidate in patients with advanced Parkinson's disease. J Neurol Neurosurg Psychiatry. 2007 May;78(5):470-5. doi: 10.1136/jnnp.2006.100016. Epub 2006 Nov 10.

  PMID: 17098845 BACKGROUND

• Espay AJ, Dwivedi AK, Payne M, Gaines L, Vaughan JE, Maddux BN, Slevin JT, Gartner M, Sahay A, Revilla FJ, Duker AP, Shukla R. Methylphenidate for gait impairment in Parkinson disease: a randomized clinical trial. Neurology. 2011 Apr 5;76(14):1256-62. doi: 10.1212/WNL.0b013e3182143537.

  PMID: 21464430 BACKGROUND

• Mendonca DA, Menezes K, Jog MS. Methylphenidate improves fatigue scores in Parkinson disease: a randomized controlled trial. Mov Disord. 2007 Oct 31;22(14):2070-6. doi: 10.1002/mds.21656.

  PMID: 17674415 BACKGROUND

• Jankovic J. Atomoxetine for freezing of gait in Parkinson disease. J Neurol Sci. 2009 Sep 15;284(1-2):177-8. doi: 10.1016/j.jns.2009.03.022. Epub 2009 Apr 9.

  PMID: 19361809 BACKGROUND

• Mirelman A, Maidan I, Deutsch JE. Virtual reality and motor imagery: promising tools for assessment and therapy in Parkinson's disease. Mov Disord. 2013 Sep 15;28(11):1597-608. doi: 10.1002/mds.25670.

  PMID: 24132848 BACKGROUND

• Gisbert R, Schenkman M. Physical therapist interventions for Parkinson disease. Phys Ther. 2015 Mar;95(3):299-305. doi: 10.2522/ptj.20130334. Epub 2014 Nov 25. No abstract available.

  PMID: 25425695 BACKGROUND

• Tomlinson CL, Patel S, Meek C, Clarke CE, Stowe R, Shah L, Sackley CM, Deane KH, Herd CP, Wheatley K, Ives N. Physiotherapy versus placebo or no intervention in Parkinson's disease. Cochrane Database Syst Rev. 2012 Jul 11;(7):CD002817. doi: 10.1002/14651858.CD002817.pub2.

  PMID: 22786482 BACKGROUND

• Thomas M, Jankovic J, Suteerawattananon M, Wankadia S, Caroline KS, Vuong KD, Protas E. Clinical gait and balance scale (GABS): validation and utilization. J Neurol Sci. 2004 Jan 15;217(1):89-99. doi: 10.1016/j.jns.2003.09.005.

  PMID: 14675615 BACKGROUND

• Williams JR, Hirsch ES, Anderson K, Bush AL, Goldstein SR, Grill S, Lehmann S, Little JT, Margolis RL, Palanci J, Pontone G, Weiss H, Rabins P, Marsh L. A comparison of nine scales to detect depression in Parkinson disease: which scale to use? Neurology. 2012 Mar 27;78(13):998-1006. doi: 10.1212/WNL.0b013e31824d587f. Epub 2012 Mar 14.

  PMID: 22422897 BACKGROUND

• Leentjens AF, Dujardin K, Pontone GM, Starkstein SE, Weintraub D, Martinez-Martin P. The Parkinson Anxiety Scale (PAS): development and validation of a new anxiety scale. Mov Disord. 2014 Jul;29(8):1035-43. doi: 10.1002/mds.25919. Epub 2014 May 23.

  PMID: 24862344 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease

Interventions

Methylphenidate; Physical Therapy Modalities; Atomoxetine Hydrochloride

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Rehabilitation; Propylamines; Amines

Study Officials

• Hubert Fernandez

  The Cleveland Clinic

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 23, 2016
• First Posted: August 25, 2016
• Study Start: January 3, 2017
• Primary Completion: December 12, 2025
• Study Completion: December 12, 2025
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)