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Weight Loss in Parkinson's Disease and Role of Small Bowel Bacterial Overgrowth

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
John K. DiBaise, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01662791
First received: August 7, 2012
Last updated: June 23, 2016
Last verified: June 2016
  Purpose
The potential role of small bowel bacterial overgrowth (SBBO) in weight loss occurring in patients with Parkinson's Disease (PD) has not previously been examined. Our hypothesis was that SBBO is an important contributor to the development of weight loss in individuals with PD. The investigators proposed to 1) examine the role of SBBO in weight loss occurring in patients with PD and 2) determine the response to its treatment with a poorly absorbed antibiotic. The investigators performed a prospective, observational case-control study (Part 1) with an open-label therapeutic component (Part 2). Cases were defined as those PD patients who experienced significant weight loss while Controls were defined as those PD patients who did not experience significant weight loss.

Condition Intervention Phase
Parkinson's Disease
Drug: Rifaximin
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Weight Loss in Parkinson's Disease and the Potential Role of Small Bowel Bacterial Overgrowth

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Number of Subjects With Small Bowel Bacterial Overgrowth (SBBO) [ Time Frame: Baseline to 2 hours ] [ Designated as safety issue: No ]
    SBBO is measured by the Hydrogen Breath Test, which measures the hydrogen and methane gas produced by bacteria in the small bowel that has diffused into the blood, then lungs for expiration. After an overnight fast, subjects ingested a solution consisting of 50 grams of glucose mixed in 150 mL of water. Immediately before ingestion of glucose and at 20-minute intervals for 2 hours following ingestion, laboratory staff collected end-expiratory breath samples and analyzed them for hydrogen and methane using a Quintron sample correction (SC) breath microlyzer. A diagnosis of SBBO was defined by an increase in expiration of 12 parts per million (ppm) or more of hydrogen and/or methane.


Secondary Outcome Measures:
  • PD-specific Quality of Life Questionnaire (PDQ-39) [ Time Frame: baseline ] [ Designated as safety issue: No ]
    The PDQ-39 is designed to address aspects of functioning and well-being for those affected by Parkinson's disease. This questionnaire is based on a multi-dimensional model of health. Eight subscale scores may be derived from the items: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognitions (4 items), communication (3 items), bodily discomfort (3 items). Patients are asked to think about their health and general well-being and to consider how often in the last month they have experienced certain events (e.g. difficulty walking 100 yards). Patients are asked to indicate the frequency of each event by selecting one of 5 options (Likert Scale): Never/occasionally/sometimes/often/always or cannot do at all. Each dimension is calculated as a scale from 0 to 100, with 0= no problem at all; 100= maximum level of problem. Sub-scale score are averaged to calculate the summary index.

  • PD-specific Quality of Life Questionnaire (PDQ-39) Over Time in Case Group [ Time Frame: Baseline and 3 months ] [ Designated as safety issue: No ]
    The PDQ-39 is designed to address aspects of functioning and well-being for those affected by Parkinson's disease. This questionnaire is based on a multi-dimensional model of health. Eight subscale scores may be derived from the items: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognitions (4 items), communication (3 items), bodily discomfort (3 items). Patients are asked to think about their health and general well-being and to consider how often in the last month they have experienced certain events (e.g. difficulty walking 100 yards). Patients are asked to indicate the frequency of each event by selecting one of 5 options (Likert Scale): Never/occasionally/sometimes/often/always or cannot do at all. Each dimension is calculated as a scale from 0 to 100, with 0= no problem at all; 100= maximum level of problem. Sub-scale score are averaged to calculate the summary index.

  • Gastrointestinal Symptom Severity Index (GISSI) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The GISSI is a validated, self-administered, multi-dimensional instrument designed to measure the frequency, severity and bothersomeness of individual GI symptoms and to provide subscale scores for interrelated symptom clusters. Factor analyses yielded 5 distinct symptom clusters that were labeled as Constipation/Difficult defecation; Abdominal Pain/Discomfort; Dyspepsia; Diarrhea/Fecal incontinence; Gastroesophageal reflux disease (GERD)/Chest symptoms; and Nausea/Vomiting. Scores could range from 0 to 100, with a higher score indicating greater severity of symptoms.

  • Gastrointestinal Symptom Severity Index (GISSI) Over Time in Case Group [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    The GISSI is a validated, self-administered, multi-dimensional instrument designed to measure the frequency, severity and bothersomeness of individual GI symptoms and to provide subscale scores for interrelated symptom clusters. Factor analyses yielded 5 distinct symptom clusters that were labeled as Constipation/Difficult defecation; Abdominal Pain/Discomfort; Dyspepsia; Diarrhea/Fecal incontinence; Gastroesophageal reflux disease (GERD)/Chest symptoms; and Nausea/Vomiting. Scores could range from 0 to 100, with a higher score indicating greater severity of symptoms.

  • Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The HADS is a self-administered 14-item questionnaire (seven for anxiety and seven for depression) Items are rated on a 4-point scale from 0-3 and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. The cut-offs used for identifying significant psychiatric distress was >/= 8. This assessment was only measured at baseline

  • Weight Change in Case Group After Treatment [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
    Weight change after treatment

  • Paffenbarger Physical Activity Questionnaire (PPAQ) [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    The PPAQ is a validated, self-administered questionnaire that asks for a recall of physical activity of physical activity over the previous 1-week. From the answers to the questions, a physical activity index (PAI) can be computed, providing an estimate of energy expenditure in kcal/week.

    The PAI can be estimated using a list of the physical activities a person performs within a time period and the amount of time spent on each activity, e.g. walking to work, light housework, swimming, carrying bricks at work, or whatever applies to an individual person. There is a value called the physical activity ratio for each activity. The list of activities is used to find the relevant values of physical activity ratios, then an overall physical activity level value for the time period is calculated, using time-weighted averages of the physical activity ratios.

    This assessment was only measured at baseline.



Other Outcome Measures:
  • Calories Consumed From Brief Block Food Frequency Questionnaire (FFQ) [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    The FFQ is a validated, self-administered semi-quantitative questionnaire used to assess differences in macronutrient, and energy intake. It was designed to provide estimates of usual and customary dietary intake. This questionnaire contains a food list of about 70 food items.

    A Food Frequency Questionnaire (FFQ) is a limited checklist of foods and beverages with a frequency response section for subjects to report how often each item was consumed over a specified period of time. Semi-quantitative FFQs collect portion size information as standardized portions or as a choice of portion sizes. Calculations for nutrient intake or calories can be estimated via computerized software programs that multiply the reported frequency of each food by the amount of nutrient or calories in a serving of that food.



Enrollment: 49
Study Start Date: September 2012
Study Completion Date: March 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Case Group
All individuals in the Case group (i.e., only the subjects who had lost weight) were offered open-label treatment with the poorly absorbed antibiotic, rifaximin, 550 mg PO twice a day (BID) for 14 days. Subjects in the case group were in the study for 3 months.
Drug: Rifaximin
All individuals in the weight loss group (i.e., only the Case group) were offered open-label treatment with the poorly absorbed antibiotic, rifaximin, 550 mg PO BID for 14 days. Treatment will not depend upon the results of the bacterial overgrowth breath test. Thus, both normal and abnormal breath test subjects received antibiotic treatment.
Other Name: Xifaxan
No Intervention: Control Group
This arm consisted of subjects with Parkinson's Disease who had not experienced significant weight loss. These patients were in the study for one day.

Detailed Description:

Part 1:

Consecutive patients seen in the Parkinson's disease clinic at Mayo Clinic in Arizona were approached to participate. After the determination of their eligibility and appropriate signed informed consent, all PD patients (i.e., both Case and Control groups) underwent the following:

  1. Assessment of demographic features, weight history and PD history
  2. PD and other medications
  3. Determination of PD severity using the Unified Parkinson's Disease rating scale
  4. Gastrointestinal Symptom Severity Index (GISSI) and modified GISSI.
  5. Determination of usual calorie and nutrient intake (Brief Block Food Frequency Questionnaire)
  6. Paffenbarger physical activity questionnaire
  7. Quality of life (SF12 and PD-specific)
  8. Hospital Anxiety and Depression Scale
  9. Glucose hydrogen breath test (SBBO test)
  10. Qualitative assessments of smell and taste

All questionnaires were completed during the 2 hour breath test.

Part 2:

All individuals in the weight loss group (i.e., only the Case group) were offered open-label treatment with the poorly absorbed antibiotic, rifaximin, 550 mg PO twice a day for 14 days. Treatment did not depend upon the results of the bacterial overgrowth breath test. Thus, both normal and abnormal breath test subjects could have received antibiotic treatment. The patient was contacted by phone 1 month after treatment at which time the presence of GI symptoms was determined and inquiry made about any adverse effects related to rifaximin use. GI symptoms, quality of life, weight measurement, and breath testing were repeated at a 3 month study visit.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria: Parkinson's Disease

Exclusion Criteria:

  1. Wheelchair-bound, akinetic individuals
  2. Tube-fed individuals
  3. Presence of dementia
  4. Unwilling or unable to complete the tests
  5. Allergic or intolerant to rifaximin
  6. Presence of chronic upper or lower gastrointestinal disorders that have symptoms that may be confused with SBBO (e.g., irritable bowel syndrome, inflammatory bowel disease, celiac disease, functional dyspepsia, gastroparesis, and chronic pancreatitis)
  7. Presence of prior surgery on the gastrointestinal tract except cholecystectomy, appendectomy or herniorrhaphy
  8. Presence of severe concomitant acute or chronic medical condition that may interfere with the completion or interpretation of the test results
  9. Women of childbearing potential. Given the age of patients with Parkinson's disease, we do not anticipate this being a large population.
  10. Use of antibiotics within 1 month of breath testing
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01662791

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: John Di Baise, MD Mayo Clinic
  More Information

Responsible Party: John K. DiBaise, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01662791     History of Changes
Other Study ID Numbers: 11-006817 
Study First Received: August 7, 2012
Results First Received: December 16, 2015
Last Updated: June 23, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
Parkinson's Disease
Small Bowel Bacterial Overgrowth
Weight Loss
Gastrointestinal
Rifaximin

Additional relevant MeSH terms:
Parkinson Disease
Weight Loss
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Body Weight Changes
Body Weight
Signs and Symptoms
Rifaximin
Rifamycins
Anti-Infective Agents
Gastrointestinal Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on September 29, 2016