Depression, Parkinson Disease, PARKINSON DISEASE (Disorder)
Conditions
Keywords
Parkinsons Disease, Depression, Probiotics, Gut Microbiome
Brief summary
This study evaluates the use of an oral multi-strain probiotic in the treatment of depression in individuals with Parkinson's Disease. Participants will be randomized to either a 12-week multi-strain probiotic treatment or placebo intervention.
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 PD have one or more depressive disorders, resulting in lower quality of life, greater care dependency, and increased caregiver burden. Gastrointestinal dysfunction is also very common in PD. Constipation is experienced by the vast majority of patients and often manifests years before onset of motor symptoms. Symptoms suggestive of irritable bowel syndrome (IBS) 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 PD. The microbiome has been linked to depression 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 (MDD) in humans. In summary, given the high rate of depression in PD, the growing evidence that probiotics may improve depression and mood disorders in non-PD populations, and the strong links between the gut microbiome and PD, we will carry out a randomized, triple-blinded, placebo-controlled study into the use of a multi-strain probiotic to improve depression and PD. Recruitment: Approximately 60 participants will be randomized to either the probiotic intervention arm or the placebo intervention arm. Participants will mainly be recruited from the Pacific Parkinson's Research Centre (PPRC) Movement Disorder Clinic at the University of British Columbia (UBC) 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, which include completing screening questionnaires and reviewing medications/medical history. Assessments: Clinical assessments of motor function, cognition and neuropsychiatric symptoms will be administered before the 12-week intervention phase, as well as following the 12-week intervention. Phone check-ins at weeks 4 and 8 during the intervention will be done to record adverse events and medication/lifestyle changes. Remote questionnaires will be sent to participants at every time point (visit 1, week 4 check-in, week 8 check-in, final visit). Blood samples and stool samples will be collected before and after the intervention. Blood (18mL) will be collected at both the first and last visits by lab staff qualified for blood drawing. Stool sample kits will be given to participants to collect at home (first sample returned via mail before start of intervention, second sample returned at final visit after intervention). The primary outcome will be the difference between the probiotic vs. placebo groups in mean Inventory of Depressive Symptomatology - Clinician-Rated (IDS-C) and mean Beck Depression Inventory 2nd edition (BDI-II) pre-/post-intervention. The primary analysis will be based on intention-to-treat. For other secondary outcomes, the between-group difference analysis will be applied to the fatigue, anxiety, PD motor function, and quality of life scores pre/post intervention, respectively. PD severity will be monitored using Parts I-IV of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Participants will be given a study journal to record their intervention doses, number of bowel movements, use of laxatives, and adverse events daily. 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.
Interventions
DIETARY_SUPPLEMENTProbiotic
Oral probiotic delivered in powdered form.
DIETARY_SUPPLEMENTPlacebo
Oral placebo delivered in powdered form.
Sponsors
University of British Columbia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, triple-blind, placebo-controlled study
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Confirmed diagnosis of Parkinson's disease based on UK Brain Bank criteria 2. Between the ages of 40-80 years 3. Mild to Moderate PD (Hoehn and Yahr stage between 1-3 in the "ON" state) 4. Mild to moderate depression (BDI-II score of 14-28 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 negative pregnancy test results at screening and baseline 6. Willingness to maintain current physical activity levels during study period 7. English proficiency
Exclusion criteria
1. Atypical Parkinsonism 2. Active suicidality 3. Active psychosis 4. Cognitive score (MoCA) of \< 21 in the "ON" state 5. Severe depression (BDI-II score \> 28 in the "ON" state) 6. Probiotic, Saccharomyces boulardii and/or antibiotic use in the past 3 months (yogurt, kefir, and other probiotic-containing foods are allowed) 7. The use of natural health products that affect depression (e.g., St. John's Wort, passion flower, gaba, 5-htp, kava, bacopa, efa's) 8. Change in the schedule of concurrent psychotherapy or brain stimulation for the treatment of mood or anxiety disorders in the last 4 weeks 9. Change in antidepressant or anxiolytic medication (including benzodiazepines) within the last 4 weeks 10. Change in Parkinson's medication within the last 2 weeks 11. Neurological disease other than PD, including Alzheimer's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, a brain tumour, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma 12. A significant immune-compromised condition due to either a health condition or use of an immune suppressant (e.g., AIDS, lymphoma, chemotherapy treatment, patients undergoing long-term systemic corticosteroid or immunosuppressant treatment) 13. A known bleeding disorder 14. Current illness (e.g., a cold or flu-like symptoms) and infections (e.g., hepatitis, HIV, gastroenteritis, fungal, or parasitic infections) 15. Allergy to corn starch or corn 16. Concurrent treatment for Parkinson's disease with Duodopa 17. Change in Deep Brain Stimulation (DBS) stimulation parameters in the last 4 weeks 18. New onset of significant psychiatric symptoms following DBS procedure that are considered likely related 19. Women who are pregnant, breastfeeding, or planning to become pregnant during the course of the trial 20. Unstable medical conditions or serious disease/conditions (e.g., cancer undergoing active treatment, poorly controlled diabetes) 21. Drug and/or substance abuse 22. The patient, in the opinion of the Investigator, is unable to adhere to the requirements of the study. This includes any patient who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a significant language barrier or cognitive impairment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inventory of Depressive Symptomatology - Clinician-Rated (IDS-C) | 13 weeks | The Inventory for Depressive Symptomatology is a measure of depressive signs and symptoms administered by a trained clinician. The score range is 0-84 points, with a higher score indicating greater levels of depressive symptomatology. |
| Beck Depression Inventory, 2nd Edition (BDI-II) | 13 weeks | The Beck Depression Inventory is a self-reported 21-question multiple-choice self-report inventory on a scale from 0-63. A higher score indicates greater characteristic attitudes and symptoms of depression. BDI-II is also used as a screening item for mild to moderate depression for this study. |
| Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR) | 13 weeks | QIDS-SR is a 16-item, self-administered questionnaire used to assess the severity of depressive symptoms over the past 7 days, based on DSM-IV criteria. QIDS-SR is a shortened version of IDS-C, but QIDS-SR is self-rated (filled in the form of a questionnaire) and IDS-C is clinician-rated (administered as a clinical assessment), so using both assessments allows us to incorporate both self-rated and clinician-rated measures. The score range is 0-27 points, with a higher score indicating greater levels of depressive symptomatology. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) | 13 weeks | The Movement Disorder Society Unified Parkinson's Disease Rating Scale is a clinical assessment of motor and non-motor symptoms in individuals with Parkinson's Disease (PD). It consists of four subscales. Subscales 1, 3, and 4 are administered by a trained individual and subscale 2 is self-reported. Each item is rated from 0 to 4. The total score can range from 0-199, with a higher score indicating greater impairment in PD. |
| Parkinson's Anxiety Scale (PAS) | 13 weeks | The Parkinson's Anxiety Scale is a 12-point observer or patient-rated scale that has three subscales: persistent anxiety, episodic anxiety, and avoidance behaviour. It is rated using a Likert scale (0-4). Possible scores range from 0-48, with a higher score indicating greater severity of anxiety symptoms. |
| Parkinson's Disease Quality of Life Questionnaire (PDQ-39) | 13 weeks | The Parkinson's Disease Quality of Life Questionnaire is a self-reported questionnaire that assesses how often people affected by Parkinson's Disease (PD) experience difficulties across 8 dimensions of daily living. It consists of 39 items and is rated on a Likert scale (0-4). Each dimension's score can range from 0-100. A higher score indicates a worse quality of life. |
| Parkinson's Disease - Cognitive Functional Rating Scale (PD-CFRS) | 13 weeks | The PD-CFRS is a short Parkinson's Disease (PD) specific questionnaire, used to explore a wide range of functional aspects suspected to be sensitive to cognitive impairment in PD. All 12 questions explore, with some examples, whether or not the patient has had trouble performing specific activities in the past few weeks. |
| Parkinson's Disease - Cognitive Rating Scale (PD-CRS) | 13 weeks | The Parkinson's Disease - Cognitive Rating Scale (PD-CRS) is a cognitive scale specifically designed to capture the whole spectrum of cognitive functions impaired over the course of Parkinson's Disease (PD). This battery is composed of a total of 9 tasks explicitly designed for a brief and separate scoring of: Frontal Subcortical tasks (sustained attention, working memory, alternating and action verbal fluency, clock drawing, immediate and delayed free recall verbal memory) and Posterior Cortical tasks (confrontation naming and clock copying). |
| Fatigue Severity Scale (FSS) | 13 weeks | The Fatigue Severity Scale is a self-reported 9-item scale which measures the severity of fatigue and its effect on a person's activities and lifestyle in patients with a variety of disorders on a scale from 1 (strongly disagree) to 7 (strongly agree). The minimum score is 9 and the maximum score is 63. A higher score indicates greater fatigue severity. |
| Montreal Cognitive Assessment (MoCA) | 13 weeks | The Montreal Cognitive Assessment test is a one-page, 30-point assessment administered by trained individuals that is used for detecting mild cognitive impairment and dementia. Score may range from 0-30 points and a lower score may indicate greater cognitive impairment. |
Countries
Canada
Contacts
CONTACTMatthew Leung, BSc
CONTACTAnnie Kuan
Outcome results
None listed