Probiotic Treatment for Depression and Associated Mood Disorders in Parkinson's Disease (ProD)
Status and phase
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Details and patient eligibility
About
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.
Full 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.
Enrollment
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Volunteers
Inclusion criteria
- Confirmed diagnosis of Parkinson's disease based on UK Brain Bank criteria
- Between the ages of 40-80 years
- Mild to Moderate PD (Hoehn and Yahr stage between 1-3 in the "ON" state)
- Mild to moderate depression (BDI-II score of 14-28 in the "ON" state)
- 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
- Willingness to maintain current physical activity levels during study period
- English proficiency
Exclusion criteria
- Atypical Parkinsonism
- Active suicidality
- Active psychosis
- Cognitive score (MoCA) of < 21 in the "ON" state
- Severe depression (BDI-II score > 28 in the "ON" state)
- Probiotic, Saccharomyces boulardii and/or antibiotic use in the past 3 months (yogurt, kefir, and other probiotic-containing foods are allowed)
- The use of natural health products that affect depression (e.g., St. John's Wort, passion flower, gaba, 5-htp, kava, bacopa, efa's)
- Change in the schedule of concurrent psychotherapy or brain stimulation for the treatment of mood or anxiety disorders in the last 4 weeks
- Change in antidepressant or anxiolytic medication (including benzodiazepines) within the last 4 weeks
- Change in Parkinson's medication within the last 2 weeks
- 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
- 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)
- A known bleeding disorder
- Current illness (e.g., a cold or flu-like symptoms) and infections (e.g., hepatitis, HIV, gastroenteritis, fungal, or parasitic infections)
- Allergy to corn starch or corn
- Concurrent treatment for Parkinson's disease with Duodopa
- Change in Deep Brain Stimulation (DBS) stimulation parameters in the last 4 weeks
- New onset of significant psychiatric symptoms following DBS procedure that are considered likely related
- Women who are pregnant, breastfeeding, or planning to become pregnant during the course of the trial
- Unstable medical conditions or serious disease/conditions (e.g., cancer undergoing active treatment, poorly controlled diabetes)
- Drug and/or substance abuse
- 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
Trial design
Primary purpose
Allocation
Interventional model
Masking
60 participants in 2 patient groups, including a placebo group
Trial contacts and locations
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Central trial contact
Annie Kuan; Matthew Leung, BSc
Data sourced from clinicaltrials.gov
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