Treating H. Pylori in Parkinson's Patients With Motor Fluctuations

Helicobacter Pylori Eradication and Motor Fluctuations in Parkinson's Disease

The purpose of this study is to determine whether treatment of H. pylori (an infection of the stomach) improves treatment effectiveness in patients with Parkinson's disease and motor fluctuations.

Study Overview

• Status: Terminated
• Conditions: Parkinson's Disease; Helicobacter Infections; Motor Fluctuations
• Intervention / Treatment: Drug: clartihromycin, amoxicillin, and omeprazole; Drug: placebo

Detailed Description

Previous investigations have demonstrated that treatment of Helicobacter pylori with antibiotics leads to improved absorption and pharmacokinetics of levodopa. This may potentially benefit patients with Parkinson's disease who have motor fluctuations, specifically excessive "off" time, when their levodopa is not working to control symptoms. We seek to identify the frequency of H. pylori infection in this population using standard lab assays and determine whether eradication with standard triple therapy results in improved clinical response to medication.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion criteria:

• Adults diagnosed with idiopathic Parkinson's disease, Hoehn & Yahr stage 2-4 in the "off" state, with no other concomitant neurologic diseases.
• Stable (≥30 days) Parkinson's disease therapy, with demonstrable medication efficacy, but with wearing off phenomenon present between levodopa doses (average off time ≥3 hours off time/day).
• Levodopa therapy required; Any formulation (e.g. Sinemet, Sinemet CR, Stalevo) is acceptable. Parkinson's disease treatment may also include any of the following medications or classes: non-ergot dopamine agonists, COMT inhibitors, MAO-B inhibitors, amantadine, anticholinergics.
• Positive for H. pylori IgG Ab by serum ELISA (before inclusion in randomized treatment arms).

Exclusion criteria:

• Current abdominal pain, unexplained nausea/vomiting, or gastrointestinal bleeding.
• History of gastric cancer, peptic ulcer, duodenal ulcer, or other gastric or duodenal lesions.
• History of previous gastric surgery.
• History of previous brain surgery for Parkinson's disease.
• Family history of gastric cancer.
• Prior treatment for H. pylori+ status.
• Recent use (previous 4 weeks) of proton-pump inhibitor, amoxicillin, or clarithromycin.
• Allergy or sensitivity to penicillin, amoxicillin, clarithromycin, or omeprazole.
• Use of drugs affecting gastric motility (e.g. domperidone, metoclopramide).
• Inability to tolerate or participate in testing in the morning in an "off" state.
• Inability to communicate effectively with study personnel in English.
• Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Active-placebo; These subject receive treatment with active triple therapy followed by treatment with placebo therapy.	Drug: clartihromycin, amoxicillin, and omeprazole; clarithromycin 500mg - i PO BID x10 days; amoxicillin 1gm - i PO BID x10 days; omeprazole 10mg - i PO BID x10 days; Other Names: Biaxin, Prilosec; Drug: placebo; placebo therapy
Other: Placebo-active; These subject receive treatment with placebo therapy followed by treatment with active triple therapy.	Drug: clartihromycin, amoxicillin, and omeprazole; clarithromycin 500mg - i PO BID x10 days; amoxicillin 1gm - i PO BID x10 days; omeprazole 10mg - i PO BID x10 days; Other Names: Biaxin, Prilosec; Drug: placebo; placebo therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
"Off" Time	Average total daily "off" time (measured by patient symptom diaries) in hours	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in UPDRS Total Scores	The Unified Parkinson Disease Rating Scale (UPDRS) is a rating tool to follow the longitudinal course of Parkinson's Disease. It is made up of the 1) Mentation, Behavior, and Mood, 2) ADL and 3) Motor sections. These are evaluated by interview. Some sections require multiple grades assigned to each extremity. A total of 199 points are possible. 199 represents the worst (total) disability), 0--no disability.	2 months
Improvement in UDPRS Part III	Improvement in UDPRS Part III (Motor) scores ("on" and "off") UPDRS III is the result of a motor examination with the scores 0-108. A decrease in the scores means improvement	2 months
Improvement in Quality of Life as Assessed by PDQ-39	The Parkinson's Disease Questionnaire (PDQ)-39 contains 39 questions addressing how often patients have experienced difficulties due to having PD in the preceding month. Items are scored from 0 (never) to 4 (always). Lower scores indicate better quality of life.	2 months
Participants With Side Effects From Study Treatment	Side effects profile	2 months

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: Michael J. Fox Foundation for Parkinson's Research
• Investigators: Principal Investigator: Jeff M Bronstein, MD, PhD, UCLA Neurology

Publications and helpful links

General Publications

• Belhoussine-Idrissi L, Boedeker EC. Helicobacter pylori infection: treatment. Curr Opin Gastroenterol. 2002 Jan;18(1):26-33. doi: 10.1097/00001574-200201000-00005.
• Pierantozzi M, Pietroiusti A, Brusa L, Galati S, Stefani A, Lunardi G, Fedele E, Sancesario G, Bernardi G, Bergamaschi A, Magrini A, Stanzione P, Galante A. Helicobacter pylori eradication and l-dopa absorption in patients with PD and motor fluctuations. Neurology. 2006 Jun 27;66(12):1824-9. doi: 10.1212/01.wnl.0000221672.01272.ba.
• Pierantozzi M, Pietroiusti A, Galante A, Sancesario G, Lunardi G, Fedele E, Giacomini P, Stanzione P. Helicobacter pylori-induced reduction of acute levodopa absorption in Parkinson's disease patients. Ann Neurol. 2001 Nov;50(5):686-7. doi: 10.1002/ana.1267. No abstract available.
• Pierantozzi M, Pietroiusti A, Sancesario G, Lunardi G, Fedele E, Giacomini P, Frasca S, Galante A, Marciani MG, Stanzione P. Reduced L-dopa absorption and increased clinical fluctuations in Helicobacter pylori-infected Parkinson's disease patients. Neurol Sci. 2001 Feb;22(1):89-91. doi: 10.1007/s100720170061.
• Wolle K, Malfertheiner P. Treatment of Helicobacter pylori. Best Pract Res Clin Gastroenterol. 2007;21(2):315-24. doi: 10.1016/j.bpg.2006.11.001.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: April 21, 2008
• First Submitted That Met QC Criteria: April 21, 2008
• First Posted (Estimate): April 22, 2008

Study Record Updates

• Last Update Posted (Actual): December 2, 2017
• Last Update Submitted That Met QC Criteria: October 31, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Helicobacter pylori; levodopa; Parkinson's disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Parkinson Disease; Helicobacter Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Amoxicillin; Omeprazole
• Other Study ID Numbers: MJJF Clinical Discovery 2007; 441437-JB-58330