Clinical trial NCT03011476: Effect of Acetylcholinesterase Inhibitors on the Gait of the Patients With Parkinson Disease
Official title: Effect of Acetylcholinesterase Inhibitors on the Gait of the Patients With Parkinson Disease Characterized by Postural Instability and Gait Disturbance
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Parkinson Disease
Lead sponsor: Kyung Hee University Hospital
Sponsor class: OTHER
First posted: 2017-01-05
Enrollment: 20
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Cholinergic deficiency in the brain can be related to gait and balance problems in Parkinson disease (PD). Recent clinical trials suggested a beneficial role of acetylcholinesterase inhibitors (AchEI) on gait in PD. In this study, the investigators are planning to study the influence of AchEI on a brain network for gait and balance in PD. As gait problem is prominent in postural instability and gait disturbance (PIGD) subtype, this study will focus on the patients with PIGD phenotype.

Detailed description: PD patients with PIGD subtype will be included.

1. Assessment:

   * Overall features of PD are assessed by Unified Parkinson Disease Rating Scale (UPDRS). Non-motor features including cognition will be assessed by standard scales. Gait and balance will be assessed by gait analysis system, which measures physiological parameters of gait such as velocity, variability and center of pressure. Positron emission tomography using 18F-fluorodeoxyglucose (FDG PET) will be done to brain activities related to gait and balance.
   * Clinical evaluation will be done at the baseline, 4th, 8th and 12th week
   * Gait analysis and FDG PET will be done at the baseline and 12th week
2. Drug dosage

   * For the first 4 weeks, 5 mg/day
   * Then, 10 mg/day for 8 weeks

Eligibility criteria: Inclusion Criteria:

* Parkinson disease diagnosed by United Kingdom Parkinson's disease Society Brain Bank Criteria
* Postural instability and gait disturbance phenotype
* Hoehn and Yahr stage ≤ 3
* Mini-Mental status examination ≥ 24

Exclusion Criteria:

* Significant motor complication affecting daily activities
* Drugs related to acetylcholine metabolism

Primary outcomes:
measure: Positron emission tomography using 18F-flurodeoxyglucose
timeFrame: Metabolic change from Baseline at 12 weeks
Secondary outcomes:
measure: Montreal Cognitive Assessment
timeFrame: Baseline assessment/ Follow-up assessment at 12th week
measure: Unified Parkinson disease rating scale (UPDRS)
timeFrame: Baseline assessment/ Follow-up assessment at 4th, 8th and 12th week
measure: Time-Up and Go
timeFrame: Baseline assessment/ Follow-up assessment at 4th, 8th and 12th week
measure: Gait analysis
timeFrame: Baseline assessment/ Follow-up assessment at 4th, 8th and 12th week
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Kyung Hee Universtiy Hospital
Study officials:
affiliation: Kyung Hee University Hospital
name: Tae-Beom Ahn, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Henderson EJ, Lord SR, Brodie MA, Gaunt DM, Lawrence AD, Close JC, Whone AL, Ben-Shlomo Y. Rivastigmine for gait stability in patients with Parkinson's disease (ReSPonD): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2016 Mar;15(3):249-58. doi: 10.1016/S1474-4422(15)00389-0. Epub 2016 Jan 13.
citation: Henderson EJ, Lord SR, Close JC, Lawrence AD, Whone A, Ben-Shlomo Y. The ReSPonD trial--rivastigmine to stabilise gait in Parkinson's disease a phase II, randomised, double blind, placebo controlled trial to evaluate the effect of rivastigmine on gait in patients with Parkinson's disease who have fallen. BMC Neurol. 2013 Dec 3;13:188. doi: 10.1186/1471-2377-13-188.
citation: Bohnen NI, Frey KA, Studenski S, Kotagal V, Koeppe RA, Scott PJ, Albin RL, Muller ML. Gait speed in Parkinson disease correlates with cholinergic degeneration. Neurology. 2013 Oct 29;81(18):1611-6. doi: 10.1212/WNL.0b013e3182a9f558. Epub 2013 Sep 27.
citation: Bohnen NI, Muller ML, Koeppe RA, Studenski SA, Kilbourn MA, Frey KA, Albin RL. History of falls in Parkinson disease is associated with reduced cholinergic activity. Neurology. 2009 Nov 17;73(20):1670-6. doi: 10.1212/WNL.0b013e3181c1ded6.
citation: Montero-Odasso M, Muir-Hunter SW, Oteng-Amoako A, Gopaul K, Islam A, Borrie M, Wells J, Speechley M. Donepezil improves gait performance in older adults with mild Alzheimer's disease: a phase II clinical trial. J Alzheimers Dis. 2015;43(1):193-9. doi: 10.3233/JAD-140759.
citation: Stebbins GT, Goetz CG, Burn DJ, Jankovic J, Khoo TK, Tilley BC. How to identify tremor dominant and postural instability/gait difficulty groups with the movement disorder society unified Parkinson's disease rating scale: comparison with the unified Parkinson's disease rating scale. Mov Disord. 2013 May;28(5):668-70. doi: 10.1002/mds.25383. Epub 2013 Feb 13.