Study of the Fecal Microbiome in Patients With Parkinson's Disease

NCT03671785 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: HSC-SPH-18-0621
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (13)

• Microbiome Diversity in Fecal Samples as Indicated by the Shannon Diversity Index

  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.

  baseline

• Microbiome Diversity in Fecal Samples as Indicated by the Shannon Diversity Index

  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.

  week 6

• Microbiome Diversity in Fecal Samples as Indicated by the Shannon Diversity Index

  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.

  week 13

• Microbiome Diversity in Fecal Samples as Indicated by the Shannon Diversity Index

  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.

  month 4

• Microbiome Diversity in Fecal Samples as Indicated by the Shannon Diversity Index

  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.

  month 6

• Microbiome Diversity in Fecal Samples as Indicated by the Shannon Diversity Index

  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.

  month 9

• Microbiome Richness in Fecal Samples as Indicated by the Number of Taxonomies per Participant

  baseline

• Microbiome Richness in Fecal Samples as Indicated by the Number of Taxonomies per Participant

  week 6

• Microbiome Richness in Fecal Samples as Indicated by the Number of Taxonomies per Participant

  week 13

• Microbiome Richness in Fecal Samples as Indicated by the Number of Taxonomies per Participant

  month 4

• Microbiome Richness in Fecal Samples as Indicated by the Number of Taxonomies per Participant

  month 6

• Microbiome Richness in Fecal Samples as Indicated by the Number of Taxonomies per Participant

  month 9

• Any untoward medical occurrence after fecal microbiota transplantation (FMT)

  9 months after treatments starts

Secondary Outcomes (34)

• Number of participants with an increase in flora diversity in fecal samples

  9 months after treatments starts

• Change in number of bowel movements per day

  Baseline, 2 weeks

• Motor function as characterized by Unified Parkinson's Disease Rating Scale (UPDRS) Total Score

  baseline

• Motor function as characterized by Unified Parkinson's Disease Rating Scale (UPDRS) Total Score

  4 months

• Motor function as characterized by Unified Parkinson's Disease Rating Scale (UPDRS) Total Score

  9 months

Study Arms (2)

Active group treated with healthy fecal microbiota

EXPERIMENTAL

Drug: PRIM-DJ2727

Placebo group

EXPERIMENTAL

Drug: Placebo oral capsule

Interventions

PRIM-DJ2727 DRUG

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

Active group treated with healthy fecal microbiota

Placebo oral capsule DRUG

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

Placebo group

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• Kelsey Research Foundation: collaborator

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Related Publications (1)

• DuPont HL, Suescun J, Jiang ZD, Brown EL, Essigmann HT, Alexander AS, DuPont AW, Iqbal T, Utay NS, Newmark M, Schiess MC. Fecal microbiota transplantation in Parkinson's disease-A randomized repeat-dose, placebo-controlled clinical pilot study. Front Neurol. 2023 Mar 2;14:1104759. doi: 10.3389/fneur.2023.1104759. eCollection 2023.

  PMID: 36937520 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Herbert L DuPont, MD

  University of Texas Health Science Center School of Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Infectious Diseases

Study Record Dates

• First Submitted: September 12, 2018
• First Posted: September 14, 2018
• Study Start: May 15, 2019
• Primary Completion: October 9, 2022
• Study Completion: October 12, 2022
• Last Updated: May 24, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)