Erythromycin in Parkinson's Disease

Not Applicable

Completed

Conditions: Parkinson's Disease
Levodopa

Interventions: Drug: placebo
Drug: Erythromycin

Registration Number: NCT02005029

Lead Sponsor: Virginia Commonwealth University

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 18

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	One time IV dose of placebo
Erythromycin	Erythromycin	One time IV dose of 100 mg Erythromycin

Primary Outcome Measures

Name	Time	Method
Gastric Emptying Time	2 weeks, between visits 2 and 3	Mean gastric emptying time in minutes as measured by SmartPill
Area Under the Curve 0-4 Hours for Plasma Levodopa After Erythromycin Versus Placebo	2 weeks, between visits 2 and 3	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.

Secondary Outcome Measures

Name	Time	Method
9-hole Peg Test Right Hand	2 weeks, between visits 2 and 3	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.
9-hole Peg Test Left Hand	2 weeks, between visits 2 and 3	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.
Five Times Sit-to-stand Test	2 weeks, between visits 2 and 3	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.
Comfortable 20 Feet Gait Speed (CGS)	2 weeks, between visits 2 and 3	Change in motor function as assessed by comfortable 20 feet gait speed (CGS)
Timed up and go Test (TUAG) Comfortable Speed	2 weeks, between visits 2 and 3	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.
Timed up and go Test (TUAG) Fast Speed	2 weeks, between visits 2 and 3	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.
Change in Dyskinesia	2 weeks, between visits 2 and 3	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).
MDS-UPDRS Part 3 (Movement Disorders Society- Unified Parkinson's Disease Rating Scale)	2 weeks, between visits 2 and 3	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).
Mean Cmax of Plasma Levodopa After Erythromycin Versus Placebo	2 weeks, between visits 2 and 3	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.