None listed
Conditions
Interventions
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-
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.
Sponsors
Drs. Andrew H. EVANS and Shen Yang LIM
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
30 Years to 80 Years
Healthy volunteers
No
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.
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.
Outcome results
None listed