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Trial registered on ANZCTR


Registration number
ACTRN12606000046505
Ethics application status
Approved
Date submitted
28/01/2006
Date registered
30/01/2006
Date last updated
30/01/2006
Type of registration
Prospectively registered

Titles & IDs
Public title
The Role of COMT (Catechol-O-Methyltransferase) Inhibition in Treating Non-Motor Fluctuations in Parkinson’s Disease
Scientific title
The Role of COMT (Catechol-O-Methyltransferase) Inhibition in Treating Non-Motor Fluctuations in Parkinson’s Disease
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Parkinson's disease (PD) 1008 0
Condition category
Condition code
Neurological 1084 1084 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Sinemet versus Stalevo
L-dopa is the most widely used and the most effective therapy to ameliorate the symptoms of Parkinson’s Disease (PD): slowness, tremor, rigidity, and postural instability. However, most PD patients who are treated with L-dopa eventually develop motor complications, such as wearing off (increasingly shorter duration of motor benefit from each dose of L-dopa).

Although fluctuations in response to L-dopa are typically defined by changes in motor signs, a wide variety of non-motor (including psychological and sensory) fluctuations may also occur and are increasingly recognized. Many patients report worse mood, anxiety and/or sensory symptoms (including pain) when “off” than when “on”. In some patients, these non-motor fluctuations are more disabling and distressing than motor fluctuations.

Standard oral formulations of L-dopa/dopa decarboxylase inhibitor (DDCI) (such as Sinemet) have a relatively short half-life. Entacapone is a catechol-O-methyltransferase (COMT) inhibitor which is widely used as an adjunct in fluctuating PD patients. It inhibits the peripheral metabolism of L-dopa and thus extends L-dopa plasma half-life and minimizes variability in plasma L-dopa levels. Clinical studies performed in patients with motor fluctuations have shown that entacapone prolongs the duration of motor response.

We aim to test the hypothesis that Stalevo (a combination tablet that includes L-dopa, carbidopa (a DDCI) and entacapone) can lead to a similar improvement in emotional state as well. We also aim to collect preliminary data on any differences in effect on pre-existing spontaneous pain.

Participants will be patients seen at the Royal Melbourne Hospital (RMH) who have PD and motor fluctuations, between the ages of 30 and 80 (inclusive).

There are 2 parts to the study:
Part 1 (L-dopa Versus Stalevo Challenge)
We propose to assess 12 patients on two mornings with a double-blind challenge of Sinemet (L-dopa 150 mg / carbidopa 50 mg) or Stalevo 150 mg.

At baseline and then at half hourly intervals for 6 hours, emotional response, parkinsonism as well as patients’ report of changes in any pre-existing spontaneous pain will be assessed using validated questionnaires and rating scales: The Positive Affect and Negative Affect Schedule (PANAS), Unified PD Rating Scale (UPDRS), modified versions of the Goetz rating scale and the Abnormal Involuntary Movements Scale (AIMS) and Gracely visual rating scales for pain severity and unpleasantness, respectively.

Part 2: 12 entacapone-naïve patients with motor fluctuations (some of whom may also be the same patients studied in Part 1) will participate in a two-week double-blind cross over study comparing Stalevo to Sinemet. Prior to this, patients will undergo a ‘dose-finding’ study over two weeks in which Stalevo will be introduced and adjusted to optimize its effect.

As for Part 1, the two regimens will be compared in terms of emotional and motor responses as well as patients’ report of changes in any pre-existing spontaneous pain. On three designated days (days 1, 4 and 7) for each of the two weeks, patients will complete an hourly (while awake) diary consisting of the PANAS, a visual analogue scale for motor state and the Gracely visual rating scales for pain severity and unpleasantness.
Intervention code [1] 869 0
None
Comparator / control treatment
Control group
Active

Outcomes
Primary outcome [1] 1449 0
The primary outcome is the PANAS
Timepoint [1] 1449 0
Measured at the above time points:
For Part 1 of the trial, this will be at half hourly intervals for 6 hours.
For Part 2 of the trial, this will be on days 1, 4 and 7 for each of the two weeks.
Secondary outcome [1] 2586 0
Secondary outcomes are the motor questionnaires and rating scales specified above and the Gracely visual rating scales.
Timepoint [1] 2586 0
For Part 1 of the trial, this will be at half hourly intervals for 6 hours.
For Part 2 of the trial, this will be on days 1, 4 and 7 for each of the two weeks.

Eligibility
Key inclusion criteria
Patients who meet ALL of the following inclusion criteria will be eligible to participate in the study:1. Patient has been diagnosed with idiopathic Parkinson disease based on the presence of a characteristic clinical history and neurological findings 2. Patient has L-dopa-associated motor response complications 3. Patient is willing to adhere to protocol requirements as evidenced by written, informed consent.
Minimum age
30 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients meeting ANY of the following exclusion criteria will not be enrolled or will be immediately excluded from the study: 1. Patients receiving entacapone previously unless the entacapone was washed out before the screening visit 2. Patients receiving treatment with monoamine oxidase inhibitors or known sensitivity to entacapone 3. Patients has clinically significant orthostatic hypotension 4. Patient has clinically significant laboratory abnormalities including renal and hepatic function elevation greater than twice the upper limit of normal 5. Patients receiving any other investigational drug 6. Patient is pregnant or breastfeeding 7. Patient has a condition (such as active drug or alcohol abuse) that, in the opinion of the investigators, would potentially interfere with patient compliance or safety.

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)
The investigators who assess patients’ responses will be blinded to patients’ allocation, via the involvement of the Pharmacy Department as an external third party responsible for assignment (i.e., allocation concealment). A computer-generated randomisation list will be drawn up by the statistician and given to the Pharmacy Department. The investigators responsible for seeing the patients will allocate the next available number on entry into the trial, and each patient will then collect his or her tablets direct from the Pharmacy Department. The code will be revealed to the investigators only once recruitment and data collection is complete
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer-generated randomisation list will be drawn up by the statistician and given to the Pharmacy Department
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2006
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 1188 0
Commercial sector/Industry
Name [1] 1188 0
Novartis
Country [1] 1188 0
Primary sponsor type
Individual
Name
Drs. Andrew H. EVANS and Shen Yang LIM
Address
Country
Secondary sponsor category [1] 1046 0
None
Name [1] 1046 0
Not Applicable
Address [1] 1046 0
Country [1] 1046 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 2503 0
Royal Melbourne Hospital - Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 2503 0
Ethics committee country [1] 2503 0
Australia
Date submitted for ethics approval [1] 2503 0
Approval date [1] 2503 0
Ethics approval number [1] 2503 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 36063 0
Address 36063 0
Country 36063 0
Phone 36063 0
Fax 36063 0
Email 36063 0
Contact person for public queries
Name 10058 0
Dr. Shen Yang LIM
Address 10058 0
Royal Melbourne Hospital
Grattan St
Parkville VIC 3050
Country 10058 0
Australia
Phone 10058 0
+61 3 93427000 Mobile: +61 419575576
Fax 10058 0
Email 10058 0
[email protected]
Contact person for scientific queries
Name 986 0
Dr. Shen Yang LIM
Address 986 0
Royal Melbourne Hospital
Grattan St
Parkville VIC 3050
Country 986 0
Australia
Phone 986 0
+61 3 93427000 Mobile: +61 419575576
Fax 986 0
Email 986 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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