Parkinson Disease
Conditions
Brief summary
The purpose of this study is to characterize the intestinal microbiome in subjects with Parkinson's disease and to determine safety and trends in improvements in diversity of colonic microbiome following administration of lyophilized PRIM-DJ2727
Interventions
DRUGPRIM-DJ2727
Twice filtered fecal microbiota product from three screened healthy donors will be lyophilized and encapsulated in enteric-coated capsules. Each dose of enteric coated capsules consists of 60 grams of stool and will be administered orally twice-weekly for 12 consecutive weeks
DRUGPlacebo oral capsule
Placebo capsule will be identical to PRIM-DJ2727 but will not contain intestinal bacteria. The placebo will consist of Lactose (spray-dried United States Pharmacopeia (USP) 64.385gm), food color, powdered Black, Brown, and Yellow in the enteric capsules. Placebo will be administered orally twice-weekly for 12 consecutive weeks
Sponsors
Kelsey Research Foundation
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
55 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Documented diagnosis of Parkinson's Disease (PD) for less than or equal to 10 years based on the United Kingdom Brain Bank Criteria and the Modified Hoehn-Yahr (H&Y) staging system of less than 3 in the OFF medicine state of at least 8-12 hours (subjects should have an asymmetric and unilateral symptoms onset). * Mild microsomia to anosmia (The University of Pennsylvania Smell Identification Test (UPSIT) less than 33), which is supportive of idiopathic PD. * Robust response to dopaminergic therapy (defined as greater than 33% reduction in symptoms (on the Unified Parkinson's Disease Rating Scale part III (UPDRS-III)) when measured in the ON medicine state compared to OFF state. * Subject has a history of constipation. * Sexually active male and female subjects of child-bearing potential agree to use an effective method of birth control during the study. * Female subjects of child-bearing potential must have a negative urine Qualitative Human chorionic gonadotropin (hCG) pregnancy test at enrollment and on the Week 1, Day 1 of the Treatment prior to administration of study drug. * Willing and able to sign an informed consent form and attend study assessments and follow ups. * Subject has an attending physician who will provide non-transplant care for the subject. * Subject is able to maintain a stable Parkinson's therapy medical regimen during participation in the study.
Exclusion criteria
* Unable to take multiple capsules orally. * Montreal Cognitive Assessment (MoCA) Score less than or equal to 23. * Atypical, vascular or drug-induced Parkinsonism. * Clinical features of psychosis or refractory hallucinations. * Unstable Parkinson's disease symptomatic therapy (defined as recent changes or additions to the PD regimen). * Compromised immune system (e.g. primary immune disorders or clinical immunosuppression due to a medical condition or medication e.g. taking systemic steroids greater than 20 milligrams (mg) a day or prednisone-equivalent) * Receipt of systemic non-topical antibiotic therapy currently or within 14 days of enrollment. * Prior Deep Brain Stimulation, or surgical intervention for PD, intravenous glutathione therapy or stem cell therapy. * History of medium or large vessel cerebrovascular accidents. * History of use of an investigational drug within 90 days prior to the screening visit. * Positive results for human immunodeficiency virus (HIV) or Hepatitis B / C. * Current history for active states of Inflammatory bowel disease, Irritable bowel syndrome, microscopic colitis, celiac disease, short gut syndrome, colostomy, colectomy, gastrointestinal fistulae or strictures. * History of significant uncontrolled systemic disease that in the opinion of the study investigator could interfere with study participation and/or objectives. * Life expectancy of less than 1 year. * In the opinion of investigator, subject for any reason, should be excluded from the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Microbiome Diversity in Fecal Samples as Indicated by the Shannon Diversity Index | baseline | The Shannon diversity index is used to characterize species diversity in a community. Shannon's index accounts for both abundance and evenness of the species present. A high index value would represent a diverse and equally distributed community, and lower values represent a less diverse community. A value of 0 would represent a community with just one species. Typical values are generally between 1.5 and 3.5. |
| Microbiome Richness in Fecal Samples as Indicated by the Number of Taxonomies per Participant | baseline | — |
| Any untoward medical occurrence after fecal microbiota transplantation (FMT) | 9 months after treatments starts | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Motor function as characterized by Unified Parkinson's Disease Rating Scale (UPDRS) Motor Score | baseline | UPDRS is a disability and impairment scale for PD progression and consists of 4 sections; I: evaluation of mentation, behavior, and mood (13 questions) II: evaluation of activities of daily living including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food (13 questions) III: motor examination (33 scores based on 18 questions with right, left or other body distributions scores) IV: motor complications (6 questions) All items have 5 response options: 0 = normal, 1 = slight (symptoms/ signs with sufficiently low frequency or intensity to cause no impact on function), 2 = mild (symptoms/ signs of frequency or intensity sufficient to cause a modest impact on function, 3 = moderate (symptoms/ signs sufficiently frequent or intense to impact considerably, but not prevent function), 4 = severe (symptoms/ signs that prevent function). Motor Score ranges from 0 to 156, with higher scores indicating a worse outcome. |
| Parkinson's disease symptoms as assessed by the Modified Hoehn and Yahr Scale | baseline | Modified H&Y scale will be used as a staging instrument to monitor progression of PD's symptoms. It defines broad categories of motor function in PD starting at Stage 0: no signs of disease to the highest stage 5: wheelchair bound or bedridden unless aided. |
| Cognitive domains characterized by using Montreal Cognitive Assessment | baseline | MoCA is a rapid screening instrument for mild cognitive dysfunction. It assess different cognitive domains: attention and concentration, executive functions, memory, language, visuo-constructional skills, conceptual thinking, calculations, and orientation. The total score ranges from 0 to 30; a score of 26 or above is considered normal. MoCA will be performed at the enrollment for baseline and the clinic visit on 9 month for study endpoint assessment, and early termination visit (if applicable). |
| Change in Sense of Smell as assessed by the University of Pennsylvania Smell Identification Test (UPSIT) | baseline, 9 months | The UPSIT is a comprehensive 40-item self-administered olfactory test that provides an absolute indication of smell loss (anosmia; mild, moderate or severe microsomia). The range of scores is 0 to 40, and a higher score indicates better olfaction |
| Qualify of life as assessed by the Parkinson's disease Questionnaire (PDQ-39) | baseline | The Parkinson's disease Questionnaire (PDQ-39) is a 39 questions self-completed questionnaire that comprises 8 domains: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items) and bodily discomfort (3 items). All items are assumed to impact Quality of Life (QoL) and must be answered to compute scores for each dimension. Questions are answered based on experiences from the preceding month using a 5-point ordinal scoring system: 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, 4 = always. Overall score ranges from 0 = never have difficulty to 100 = always have difficulty. For each of the 8 domains, the domain score is the sum of scores in the domain divided by the maximum possible score of all items in the domain, multiplied by 100. The overall score is the sum of all 8 domain scores divided by 8. |
| Quality of Life as assessed by the Parkinson Disease Non-Motor Symptoms (PD NMS) Questionnaire | baseline | The range of scores is 0 to 30. A score of under 10 is mild, 10-20 moderate and over 20 severe. |
| Number of participants who changed required PD symptomatic therapy after treatment | 9 months after treatment | — |
| Number of participants with an increase in flora diversity in fecal samples | 9 months after treatments starts | — |
| Anxiety as assessed by the Parkinson Anxiety Scale (PAS) | baseline | The Parkinson Anxiety Scale (PAS) is an anxiety measure scale for use in PD patients. This is a 12-item observer or patient-rated scale with three subscales, for persistent and episodic anxiety, and avoidance behavior. Items are scored on a 5-point Likert scale, with '0' meaning 'not or never' and '4' meaning 'severe or almost always'. Total score ranges from 0 to 48, with higher scores indicating worse outcomes. |
| Depression as assessed by the Geriatric Depression Scale Short form (GDS-SF) | baseline | The Geriatric Depression Scale Short form (GDS-SF) is 15-item screening tool that is used to identify depression in older adults. The total score is 0 to 15, with a score of 5 or greater suggesting depression. |
| Change in gastric emptying time (GET) as assessed by the Smart Pill® (SP) Wireless pH/pressure recording capsule | baseline, 13 weeks | Smart Pill will be used to assess gastrointestinal dysmotility in PD patients before and after 12- week treatment. Smart Pill will be administered first during the run-In period clinic visit and again at Week 13 clinic visit following the completion of 12-week treatment. After an overnight fast, subjects will ingest the Smart Pill capsule with a nutrient bar (Smart Bar, 243 kcal) and will be instructed to wear a data receiver for 5 days or until the expulsion of the Smart Pill. After expulsion of the Smart Pill in approximately 5 days, subject will return the data receiver. Data receiver can either be dropped by or mailed via FedEx to the study site. Changes in gastric emptying time (GET), small bowel transit time (SBTT), colon transit time (CTT), small/ large bowel transit time (SLBTT) and whole gut transit time (WGTT) will be assessed by parameters established by the company providing the Smart Pill capsule. |
| Change in small bowel transit time (SBTT) as assessed by the Smart Pill® (SP) Wireless pH/pressure recording capsule | baseline, 13 weeks | Smart Pill will be used to assess gastrointestinal dysmotility in PD patients before and after 12- week treatment. Smart Pill will be administered first during the run-In period clinic visit and again at Week 13 clinic visit following the completion of 12-week treatment. After an overnight fast, subjects will ingest the Smart Pill capsule with a nutrient bar (Smart Bar, 243 kcal) and will be instructed to wear a data receiver for 5 days or until the expulsion of the Smart Pill. After expulsion of the Smart Pill in approximately 5 days, subject will return the data receiver. Data receiver can either be dropped by or mailed via FedEx to the study site. Changes in gastric emptying time (GET), small bowel transit time (SBTT), colon transit time (CTT), small/ large bowel transit time (SLBTT) and whole gut transit time (WGTT) will be assessed by parameters established by the company providing the Smart Pill capsule. |
| Change in colon transit time (CTT) as assessed by the Smart Pill® (SP) Wireless pH/pressure recording capsule | baseline, 13 weeks | Smart Pill will be used to assess gastrointestinal dysmotility in PD patients before and after 12- week treatment. Smart Pill will be administered first during the run-In period clinic visit and again at Week 13 clinic visit following the completion of 12-week treatment. After an overnight fast, subjects will ingest the Smart Pill capsule with a nutrient bar (Smart Bar, 243 kcal) and will be instructed to wear a data receiver for 5 days or until the expulsion of the Smart Pill. After expulsion of the Smart Pill in approximately 5 days, subject will return the data receiver. Data receiver can either be dropped by or mailed via FedEx to the study site. Changes in gastric emptying time (GET), small bowel transit time (SBTT), colon transit time (CTT), small/ large bowel transit time (SLBTT) and whole gut transit time (WGTT) will be assessed by parameters established by the company providing the Smart Pill capsule. |
| Change in small/large bowel transit time (SLBTT) as assessed by the Smart Pill® (SP) Wireless pH/pressure recording capsule | baseline, 13 weeks | Smart Pill will be used to assess gastrointestinal dysmotility in PD patients before and after 12- week treatment. Smart Pill will be administered first during the run-In period clinic visit and again at Week 13 clinic visit following the completion of 12-week treatment. After an overnight fast, subjects will ingest the Smart Pill capsule with a nutrient bar (Smart Bar, 243 kcal) and will be instructed to wear a data receiver for 5 days or until the expulsion of the Smart Pill. After expulsion of the Smart Pill in approximately 5 days, subject will return the data receiver. Data receiver can either be dropped by or mailed via FedEx to the study site. Changes in gastric emptying time (GET), small bowel transit time (SBTT), colon transit time (CTT), small/ large bowel transit time (SLBTT) and whole gut transit time (WGTT) will be assessed by parameters established by the company providing the Smart Pill capsule. |
| Change in whole gut transit time (WGTT) as assessed by the Smart Pill® (SP) Wireless pH/pressure recording capsule | baseline, 13 weeks | Smart Pill will be used to assess gastrointestinal dysmotility in PD patients before and after 12- week treatment. Smart Pill will be administered first during the run-In period clinic visit and again at Week 13 clinic visit following the completion of 12-week treatment. After an overnight fast, subjects will ingest the Smart Pill capsule with a nutrient bar (Smart Bar, 243 kcal) and will be instructed to wear a data receiver for 5 days or until the expulsion of the Smart Pill. After expulsion of the Smart Pill in approximately 5 days, subject will return the data receiver. Data receiver can either be dropped by or mailed via FedEx to the study site. Changes in gastric emptying time (GET), small bowel transit time (SBTT), colon transit time (CTT), small/ large bowel transit time (SLBTT) and whole gut transit time (WGTT) will be assessed by parameters established by the company providing the Smart Pill capsule. |
| Number of participants with worsening of PD symptoms or other potential microbial-mediated disorders | 9 months after treatment | — |
| Change in number of bowel movements per day | Baseline, 2 weeks | The 2 week data point will be the average of bowel movements per day over the two weeks after initiation of treatment. |
| Motor function as characterized by Unified Parkinson's Disease Rating Scale (UPDRS) Total Score | baseline | UPDRS is a disability and impairment scale for PD progression and consists of 4 sections; I: evaluation of mentation, behavior, and mood (13 questions) II: evaluation of activities of daily living including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food (13 questions) III: motor examination (33 scores based on 18 questions with right, left or other body distributions scores) IV: motor complications (6 questions) All items have 5 response options: 0 = normal, 1 = slight (symptoms/ signs with sufficiently low frequency or intensity to cause no impact on function), 2 = mild (symptoms/ signs of frequency or intensity sufficient to cause a modest impact on function, 3 = moderate (symptoms/ signs sufficiently frequent or intense to impact considerably, but not prevent function), 4 = severe (symptoms/ signs that prevent function). Total Score ranges from 0 to 260, with higher scores indicating a worse outcome. |
Countries
United States
Outcome results
None listed