Erythromycin in Parkinson's Disease

Study Overview
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Brief Summary
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Gastroparesis (slow stomach emptying) is a common feature of Parkinson's Disease. Levodopa (Sinemet), a common medication for Parkinson's Disease, can make gastroparesis worse. Gastroparesis effects how the levodopa is absorbed and used by the body. This study will explore the possibility of using Erythromycin, a drug commonly used (off label) for gastroparesis, along with levodopa to determine if there is improved levodopa absorption and motor function.

Detailed Description
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Participants will be required to make four visits for evaluation. Visit 1 is a screening visit, participants will receive the study drug or a placebo during visits 2 and 3, and visit 4 is a follow up visit. Participants will provide blood and urine samples during the visits. Participants will also be required to complete questionnaires and a series of motor tests.

Official Title
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Erythromycin in Parkinson's Disease: A Pilot Study of Its Effects on Levodopa Pharmacokinetics and Pharmacodynamics

Conditions
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Parkinson's Disease, Levodopa

Intervention / Treatment
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* Drug: Erythromycin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have a definitive diagnosis of Parkinson's Disease (per United Kingdom brain bank criteria), Hoehn and Yahr stage 1-3, must exhibit unequivocal levodopa responsiveness must be able to distinguish between the off versus on state Subjects must be on a stable dose of levodopa for at least 28 days prior to enrollment and should be anticipated to maintain a stable dose throughout both study periods Subjects may be on concomitant therapy with Monoamine oxidase B inhibitors, entacapone, and amantadine, though the doses of these medications must have remained stable for at least 28 days prior to enrollment and must be expected to remain stable throughout both study periods. Exclusion Criteria: History of deep brain stimulation for Parkinson Disease History of ablative (tissue removal) surgery for Parkinson Disease Presence of dementia (MMSE<25) Presence of active psychosis History of any chronic gastrointestinal diseases History of any prior gastrointestinal surgeries except for appendectomy, cholecystectomy, and hysterectomy Any gastrointestinal surgeries in the past 3 months Severe dysphagia (difficulty swallowing) to pills or food History of physiological or mechanical gastrointestinal obstruction History of strictures or fistulae (abnormal or narrow connections) along the gastrointestinal tract History of gastric bezoars (undigested mass) Allergy to wheat, soy, milk, or nuts Presence of portable electromechanical devices such as pacemaker, defibrillator, or infusion pump Female subjects who are pregnant or lactating Symptomatic orthostatic hypotension (low blood pressure) Diabetes Presence of symptomatic anemia Abnormal liver or kidney function Cardiac arrhythmia (past or present) or abnormal QT interval on entrance EKG Known hypersensitivity to any of the study drugs Subjects receiving certain medications during specified time frames

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>One time IV dose of placebo | Drug: placebo<br> <br> |
| Experimental: Erythromycin<br>One time IV dose of 100 mg Erythromycin | Drug: Erythromycin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastric Emptying Time | Mean gastric emptying time in minutes as measured by SmartPill | 2 weeks, between visits 2 and 3 | 
| Area Under the Curve 0-4 Hours for Plasma Levodopa After Erythromycin Versus Placebo | Mean Area under the Curve 0-4 hours for plasma levodopa after erythromycin versus placebo. Plasma samples were collected at the following times post-levodopa dose: 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, and 240 minutes. | 2 weeks, between visits 2 and 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 9-hole Peg Test Right Hand | Change in motor function as assessed by 9-hole peg test for upper extremity manipulation/dexterity. This test measures the total time required to place and remove 9 holes in a pegboard. Each hand is tested separately. | 2 weeks, between visits 2 and 3 | 
| 9-hole Peg Test Left Hand | Change in motor function as assessed by 9-hole peg test for upper extremity manipulation/dexterity. This test measures the total time required to place and remove 9 holes in a pegboard. Each hand is tested separately. | 2 weeks, between visits 2 and 3 | 
| Five Times Sit-to-stand Test | Change in motor function as measured by Five times sit-to-stand test. This test measures the total time to complete 5 repetitions of sit to stand. | 2 weeks, between visits 2 and 3 | 
| Comfortable 20 Feet Gait Speed (CGS) | Change in motor function as assessed by comfortable 20 feet gait speed (CGS) | 2 weeks, between visits 2 and 3 | 
| Timed up and go Test (TUAG) Comfortable Speed | Change in motor function as assessed by timed up and go test (comfortable speed). This test measures the total time to stand from a chair, walk 10 feet, and return to sitting. | 2 weeks, between visits 2 and 3 | 
| Timed up and go Test (TUAG) Fast Speed | Change in motor function as assessed by timed up and go test (fast speed). This test measures the total time to stand from a chair, walk 10 feet, and return to sitting. | 2 weeks, between visits 2 and 3 | 
| Change in Dyskinesia | Mean total AIMS (Abnormal Involuntary Movements Scale) score after receiving erythromycin minus mean total AIMS score after receiving placebo. The AIMS test has a total of twelve items rating involuntary movements of various areas of the patient's body. Ten of the items are rated on a five-point scale of severity from 0-4. The scale is rated from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe). Two of the items are not scored. Total score range is from 0 to 40. Higher scores represent more severe dyskinesia (a worse outcome). | 2 weeks, between visits 2 and 3 | 
| MDS-UPDRS Part 3 (Movement Disorders Society- Unified Parkinson's Disease Rating Scale) | Part 3 of this scale is a standardized physical assessment that quantifies the total burden of motor symptoms in Parkinson's disease patients. Each of the 18 items on the scale is rated from 0 (none, 1 (slight), 2 (mild), 3 (moderate) and 4 (severe). Scores range from 0-72. Higher scores represent a more severe burden of motor symptoms (a worse outcome). | 2 weeks, between visits 2 and 3 | 
| Mean Cmax of Plasma Levodopa After Erythromycin Versus Placebo | Mean Cmax of plasma levodopa after erythromycin versus placebo. Plasma samples were collected at the following times post-levodopa dose: 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, and 240 minutes. | 2 weeks, between visits 2 and 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's Disease, Levodopa, motor fluctuations, gastroparesis