High and Low Dose Treatment of Carbidopa in Parkinson's Disease

Official Title: “A Randomized Controlled Trial of Four Week Outpatient Treatment of Parkinson's Disease Comparing High and Low Dose Carbidopa.”

1. Briefly describe the purpose of this protocol: - The purpose of this study is to see how low dose vs. high dose of the study drug, carbidopa, effect movement in subjects with Parkinson's disease. The low dose of the study drug is 75 mg and the high dose is 450mg.

2. Briefly describe the procedures subjects will undergo: - Subjects will take part in 2 screening visits one week apart to determine eligibility. Subjects will be randomly chosen to start either high or low dose carbidopa and take it for 4 weeks. Subjects will be called 2, 4, and 6 or 7 days after this visit to ask how they are doing after starting this dose of study drug.

The investigators will leave subjects a message if the investigators cannot reach them. If there are any problems, the investigators will schedule them to come to the clinic within the next 2 days. - Subjects will have an outpatient visit 2 weeks after screening and a hospital admission 2 weeks after that. At the hospital, subjects will stay for 3 days.

They will have blood drawn and their Parkinson's disease assessed by a finger tapping exercise, timing their walking, and looking at their uncontrolled movements. - The subject will then receive the opposite dose of carbidopa for 4 weeks. Subjects will be called 2, 4, and 6 or 7 days after this visit to ask how they are doing after starting this dose of study drug. The investigators will leave them a message if we cannot reach them. If there are any problems, the investigators will schedule them to come to the clinic within the next 2 days. - The outpatient visit and hospital admission will repeat again. At the end of the second hospital admission, treatment on the study is over and subjects will go back to their original Parkinson's disease medications. The study will end with a follow up phone call or clinic visit 2 - 4 weeks after the final hospital admission.

3. If applicable, briefly describe survey/interview instruments used. - Subjects will fill out a daily diary that asks about their movement throughout the day for 3 days before they come to the Oregon Clinical and Translational Research Institute.

4. Briefly describe how the data will be analyzed to address the purpose of the protocol. - Finger tapping rates will be compared between high and low dose study drug use to see if one group has slower rates than the other.

Intervention(s) in this Clinical Trial

• Drug: Carbidopa-Levodopa
  • For the first four weeks, the patient will receive carbidopa 75mg daily plus placebo, plus levodopa at level the patient was taking prior to start of study. For the last 4 weeks, the patient will receive carbidopa 450mg daily plus previous dose of levodopa
• Drug: Carbidopa- Levodopa
  • For the first four weeks, the patient will receive carbidopa 450mg daily plus levodopa at level the patient was taking prior to start of study. For the last 4 weeks, the patient will receive carbidopa 75mg daily plus placebo, plus previous dose of levodopa

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Subjects will be randomly chosen to receive high dose carbidopa plus levodopa and take it for 4 weeks. After a hospital inpatient stay, the subject will then receive a low dose carbidopa plus levodopa for 4 weeks followed by one last hospital inpatient stay. The hospital stays include IV administration of the levodopa.
• Active Comparator: 2
  • Subjects will be randomly chosen to receive low dose carbidopa plus levodopa and take it for 4 weeks. After a hospital inpatient stay, the subject will then receive high dose carbidopa plus levodopa for 4 weeks followed by one last hospital inpatient stay. The hospital stays will include IV administration of levodopa.

Primary Measures

• Bradykinesia, assessed by alternate finger tapping
  • Time Frame: Week 5 and week 9
    Safety Issue?: No

Secondary Measures

• Pharmacokinetics of levodopa
  • Time Frame: week 5 and week 9
    Safety Issue?: No

Inclusion Criteria:

• Idiopathic Parkinson's disease patient as judged by history and physical examination.
• Increase in finger tapping rate of most affected side (back and forth between two counters, as explained in the Materials and Methods section)
• Willing to hold PD meds each night for 3 days.
• Symptoms of PD for at least 3 years, and on carbidopa/levodopa therapy for at least 1 year.
• Subjects must be taking a minimum of 600mg of levodopa a day

Exclusion Criteria:

• Severe limitation of downgaze, balance problems, history of early falling, or other signs suggestive of atypical parkinsonian syndrome.
• Substantial history of cardiac or cerebrovascular disease that in the investigators' judgment would lead to risk of adverse outcomes.
• Pregnancy or breast-feeding, or highly likely to become pregnant before the inpatient admission. Positive B-HCG at the time of the screening visit.
• Age <35 or >85.
• Hypotensive (i.e. sustained sitting sbp <95) or bradycardic (sustained hr <54) at the initial visit, or by history.
• Very frequent and treatment refractory nausea and/or vomiting.
• Sustained or significant hypokalemia or hypomagnesemia.
• Refractory hypertension, as determined by the investigators.
• Heavy alcohol use, as determined by clinical history of current alcoholism.
• Renal failure or severe renal insufficiency as determined by the investigators.
• Substantial hepatic impairment, by history or as determined by the investigators.
• Hemoglobin <11 g/dl. Absolute neutrophils count <1000 per µl. Platelets <120,000 per µl.
• Psychosis or use of antipsychotic medications. Current illicit drug abuse.
• Mini mental status examination (MMSE) score < 24 so that they would be
• Any medical or psychiatric condition that could pose a risk to the individual or compromise their ability to participate in the study.
• Deep brain stimulator in place

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 35 Years

Maximum Age for this Clinical Trial: 85 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Oregon Health and Science University Other

Overall Clinical Trial Officials and Contacts

John G Nutt, MD Principal Investigator Oregon Health and Science University  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00745277

Study ID Number: eIRB#4133

ClinicalTrials.gov Identifier: NCT00745277

Health Authority: United States: Food and Drug Administration