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Trial registered on ANZCTR


Registration number
ACTRN12614000355673
Ethics application status
Approved
Date submitted
25/03/2014
Date registered
2/04/2014
Date last updated
2/04/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the effect of Rasagiline on freezing of gait in Parkinson’s disease using accelerometry and functional MRI.
Scientific title
Can Rasagiline alleviate symptoms of freezing of gait in patients with Parkinson's disease?
Secondary ID [1] 284319 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Freezing of gait in Parkinson's disease 291467 0
Condition category
Condition code
Neurological 291835 291835 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study is aimed to determine whether Rasagiline reduces the frequency and severity of freezing of gait (FOG) in Parkinson’s disease (PD). PD patients suffering from FOG will be randomized to either Rasagiline, 1mg once a day, orally ingested, or an oral placebo capsule for 12 consecutive weeks. After the 12 week intervention, the patients' gait variables will be evaluated and compared to their gait variables prior the treatment. To monitor adherence to treatment, participants must return their left over drug tablets at their last visit to enable pill count.
Intervention code [1] 289038 0
Treatment: Drugs
Comparator / control treatment
Patients in the control group will receive oral placebos (capsules identical to those with medication in the intervention groups, containing glucose and lactose), once daily for 12 consecutive weeks.
All patients will continue their usual treatment.
Control group
Placebo

Outcomes
Primary outcome [1] 291753 0
Blinded assessment of time spend frozen during the Timed Up and Go assessment analyzed using accelerometry and video recordings at the end of the study compared to prior to treatment and to placebo.
Timepoint [1] 291753 0
Assessed within the final 2 weeks of the treatment period and compared to the assessment prior to the investigation.
Secondary outcome [1] 307414 0
Changes in the BOLD response on functional MRI at the end of the study compared to prior to treatment and to placebo.
Timepoint [1] 307414 0
Assessed within the final 2 weeks of the treatment period and compared to the assessment prior to the investigation.
Secondary outcome [2] 307415 0
Changes in the performance on the Trail Making Test part A and B; clinician-administered tests of processing speed and flexible thinking
Timepoint [2] 307415 0
Assessed within the final 2 weeks of the treatment period and compared to the assessment prior to the investigation.

Eligibility
Key inclusion criteria
Patients diagnosed with PD according to the United Kingdom Brain Bank clinical criteria and confirmed by a trained neurologist.
Age over 18
Mini-Mental State Examination>/=24
Screening questionnaire criteria (FOG-Q) with a positive score on item 3.
FOG determined by the TUG prior to randomisation.
Stable medications for 1 month prior to randomisation.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Significant psychiatric disorder or cognitive impairment (MMSE< 24)
Current use of Rasagiline or medications that should be avoided with the concurrent use of Rasagiline, unless washout of more than four weeks.
Galactose intolerance, LAPP lactase deficiency or glucose-galactose malabsorption.
Any significant liver, kidney or autoimmune disease.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will be approached via telephone based on previous medical and neuropsychological assessments at the PD Research Clinic to see if they are interested in taking part in the trial. Other participants may approach the clinic based on advertisement of the trial. Participants will then be sent out detailed information regarding the project in addition to consent forms. Participants will be allocated to groups using a blocked randomisation method conducted by a member of the clinical research team who is not in any way involved in the recruitment, assessment or training in the study.
After baseline assessments, participants will receive the tablets (either Rasagiline or placebo) prepared by a person who is not involved in the assessment or training in the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomized at the time of the baseline assessment using a simple randomization table created by computer software and allocated by a blinded researcher not involved in trial recruitment, data gathering, assessments or training. Randomization will occur in 1:1 ratio in random blocks. Patients will be allocated a unique ID code in sequential, ascending chronological order.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
A mixed model design will be used. The trial will be analysed on an intention-to-treat basis (Placebo or 1mg Rasagiline). Drug randomisation and time will be the fixed factors. Event rates from the first week prior treatment and week 12 after treatment will be used in the mixed model analysis of variance to help characterise individual patients variability (individual patients will be random factors). For the primary test of efficacy in the model we will test whether Rasagiline causes a reduction in time spend frozen than placebo over the last 12 weeks of the treatment period. Twenty patients will be randomised in each strata to have sufficient completers in this efficacy trial assuming a dropout rate of 10% to detect a reduction in the average amount spend frozen of 30%. With 18 completers in each strata, we will have 90% power with alpha set at 5% to detect this 30% relative improvement.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2014
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 288957 0
Commercial sector/Industry
Name [1] 288957 0
Lundbeck Australia
Country [1] 288957 0
Australia
Primary sponsor type
Individual
Name
A/Prof Simon Lewis
Address
Brain & Mind Research Institute,
100 Mallett Street,
Camperdown, Sydney,
New South Wales, 2050
Country
Australia
Secondary sponsor category [1] 287636 0
None
Name [1] 287636 0
Address [1] 287636 0
Country [1] 287636 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290768 0
Human Research Ethics Committee, University of Sydney
Ethics committee address [1] 290768 0
Level 6
Jane Foss Russell Building G02
University of Sydney,
New South Wales, 2006
Ethics committee country [1] 290768 0
Australia
Date submitted for ethics approval [1] 290768 0
Approval date [1] 290768 0
Ethics approval number [1] 290768 0
2013/1030

Summary
Brief summary
We will evaluate whether Rasagiline is an effective treatment to alleviate symptoms of freezing of gait (FOG) in Parkinson’s disease. 40 patients with FOG will be randomised to either Rasagiline or placebo arms. Treatment response will be assessed by video recordings and accelerometry of specific walking tasks (Timed up and Go test), taken before and after the intervention. In addition, functional brain imaging whilst patients perform a validated virtual reality gait paradigm will be used to determine the brain activation patterns associated with improvements in FOG. The use of brain imaging will also allow us to see why patients might have differential responses to therapy. Identifying the nature of these relationships will hopefully advance our understanding of freezing.
Trial website
Trial related presentations / publications
Chen, J. J. & Ly, A-V. Rasagiline: A second-generation monoamine oxidase type B-inhibitor for the treatment of Parkinson's disease. Am J Health-Syst Pharm. 2006; 63: 915-928.

Parkinson Study Group. A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study. Arch Neurol. 2002; 59:1937-43.

Parkinson Study Group. A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Arch
Neurol. 2004; 61:561-6.

Rascol O, Brooks DJ, Melamed E et al. Rasagiline as an adjunct to levodopa in patients with Parkinson’s disease and
motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. Lancet. 2005; 365:947-54.

Parkinson Study Group. A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations. The PRESTO Study. Arch Neurol. 2005; 62:241-8.

Lewis, S. J. G. & Barker, R. A. A pathophysiological model of freezing of gait in Parkinson's disease. Parkinsonism Rel Disord. 2009; 15(5): 333-8

Shine, J. M., Matar, E., Ward, P. B., et al. Exploring the cortical and subcortical functional magnetic resonance imaging changes associated with freezing in Parkinson’s disease. Brain. 2013; 136(4): 1204-1215
Public notes

Contacts
Principal investigator
Name 47194 0
A/Prof Simon Lewis
Address 47194 0
Brain & Mind Research Institute
100 Mallett Street,
Camperdown, Sydney,
New South Wales, 2050
Country 47194 0
Australia
Phone 47194 0
+61 2 9351 0702
Fax 47194 0
Email 47194 0
[email protected]
Contact person for public queries
Name 47195 0
Simon Lewis
Address 47195 0
Brain & Mind Research Institute
100 Mallett Street,
Camperdown, Sydney,
New South Wales, 2050
Country 47195 0
Australia
Phone 47195 0
+61 2 9351 0702
Fax 47195 0
Email 47195 0
[email protected]
Contact person for scientific queries
Name 47196 0
Simon Lewis
Address 47196 0
Brain & Mind Research Institute
100 Mallett Street,
Camperdown, Sydney,
New South Wales, 2050
Country 47196 0
Australia
Phone 47196 0
+61 2 9351 0702
Fax 47196 0
Email 47196 0
[email protected]

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