Clinical trial NCT03968133: Treating Anxiety in Parkinson's Disease With a Multi-Strain Probiotic
Official title: Treating Anxiety in Parkinson's Disease With a Multi-Strain Probiotic - a Randomized, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Parkinson Disease
Anxiety
Keywords: probiotic
mood
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: The W. Garfield Weston Foundation
First posted: 2019-05-30
Enrollment: 61
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, triple-blind, placebo-controlled study
Primary purpose: TREATMENT

Brief summary: This study evaluates the use of an oral multi-strain probiotic in the treatment of anxiety in individuals with Parkinson's Disease. Participants will be randomized to either 12-week multi-strain probiotic treatment or placebo.

Detailed description: Parkinson's disease (PD) is a complex condition that carries a high burden of neuropsychiatric comorbidities. About a third of individuals living with Parkinson's disease have one or more anxiety disorders, resulting in lower quality of life, greater care dependency, and increased caregiver burden. Gastrointestinal dysfunction is very common in Parkinson's. Constipation is experienced by the vast majority of patients and often manifests years before onset of motor symptoms, symptoms suggestive of irritable bowel syndrome are also commonly found in PD. Increased intestinal permeability has been demonstrated in PD. Impaired intestinal barrier function can lead to chronic systemic low-grade inflammation, which has been strongly associated with mood disorders. Several lines of evidence suggest a link between the gut microbiome and Parkinson's disease.

The microbiome has been linked to anxiety both in human and animal studies. Several studies have found beneficial effects of probiotics on mood disorders in non-PD populations, including stress and depressive behaviour in animal models, and sad mood reactivity and major depressive disorder in humans. Specifically regarding anxiety, probiotics have shown benefits in several animal models; human probiotic trials have demonstrated improvements in psychological distress and anxiety in healthy controls, in mothers experiencing postpartum depression and anxiety and in individuals afflicted with IBS-related anxiety without PD.

In summary, given the high rate of anxiety in PD, the growing evidence that probiotics may improve anxiety and mood disorders in non-PD populations, and the strong links between the gut microbiome and PD, we will carry out a randomized, blinded, placebo-controlled study into the use of a multi-strain probiotic to improve anxiety and Parkinson's disease.

Recruitment: Approximately 72 participants will be randomized to either the probiotic intervention arm or placebo treatment. Participants will mainly be recruited from the Pacific Parkinson's Research Centre movement disorder clinic at the University of British Columbia in Vancouver.

Participants will receive a detailed description of the study and will need to provide informed consent for participation in the study. Participants will be screened for inclusion and exclusion criteria.

Assessments: Clinical assessments of motor function, cognition and neuropsychiatric symptoms will be done before the 12 week intervention phase as well as following after the 12 week intervention with regular check ins during the course of the intervention. Blood samples and stool samples will be collected before and after the intervention.

The primary outcome will be the difference between the probiotic vs. placebo groups in mean Parkinson's Anxiety Scale (PAS) score pre/post-intervention. The primary analysis will be based on intention-to-treat. Secondary analyses for anxiety will include assessing the proportion of participants with a post-intervention PAS of ≤13 in each group. For other secondary outcomes, the between-group difference analysis will be applied to the fatigue, depression, PD motor function, severity (UPDRS I-III) and quality of life scores pre/post intervention, respectively. Adverse events, tolerability and drop-out rates will be registered and overall rates compared between the intervention groups. Furthermore, differences and changes in blood markers and microbiome composition will be assessed.

Eligibility criteria: Inclusion Criteria

1. Confirmed diagnosis of Parkinson's disease based on Queen Square Brain Bank criteria
2. Between ages 40-80
3. Hoehn and Yahr stage between 1-3 (mild to moderate PD) in the "ON" state
4. Anxiety (PAS score ≥14, MDS-UPDRS Part 1.4 score ≥ 2, and/or clinical diagnosis of anxiety based on the MINI clinical interview in the "ON" state)
5. Women of childbearing potential must agree to use a medically approved method of birth control (e.g. hormonal contraceptives, intrauterine devices, vasectomy/tubal litigation, barrier methods and double barrier method) and must have a negative urine pregnancy test result at screening and baseline
6. Willingness to maintain current physical activity levels during study period

Exclusion criteria

1. Atypical parkinsonism
2. Active suicidality
3. Active psychosis
4. Cognitive score (MoCA) of \<21 in "ON" state
5. BDI-II score above 28 in "ON" state
6. Probiotic, sacchromyces boulardii and/or antibiotic usage in the past 3 months
7. Anti-inflammatory drug usage more than twice a week (e.g. corticosteroids, naproxen, ibuprofen, celecoxib). Use of daily 81 mg ASA permitted
8. The use of natural health products that affect depression (e.g. St. John's Wort, passion flower)
9. Concurrent psychotherapy or brain stimulation for the treatment of mood disorders
10. Change in antidepressant or anxiolytic medication (including benzodiazepines) within the last 4 weeks
11. Change in Parkinson's medication within the last 2 weeks
12. Neurological disease other than PD, including Alzheimer's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, a brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma
13. An immune-compromised condition (e.g. AIDS, lymphoma, patients undergoing long term corticosteroid treatment)
14. A bleeding disorder
15. Current illness (for example a cold or flu like symptoms) and infections (for example hepatitis, HIV, gastroenteritis, fungal, or parasitic infections)
16. Allergy to corn starch or corn
17. Concurrent treatment for Parkinson Disease with Duodopa or Deep Brain Stimulation (DBS)
18. Women who are pregnant, breast feeding, or planning to become pregnant during the course of the trial
19. Unstable medical conditions or serious disease/conditions (e.g. cancer, cardiovascular, renal, lung, diabetes)
20. Drug and/or substance abuse

Primary outcomes:
measure: Parkinson's Anxiety Scale (PAS)
timeFrame: 13 weeks
Secondary outcomes:
measure: Beck Depression Inventory (BDI)
timeFrame: 13 weeks
measure: Parkinson's Disease Quality of Life Questionnaire (PDQ-39)
timeFrame: 13 weeks
measure: Fatigue Severity Scale (FSS)
timeFrame: 13 weeks
measure: Montreal Cognitive Assessment
timeFrame: 13 weeks
measure: Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
timeFrame: 13 weeks
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Pacific Parkinson's Research Centre
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Silke Appel-Cresswell, MD
role: PRINCIPAL_INVESTIGATOR
References: