Characterization of Fecal Microbiome Changes After Administration of PRIM-DJ2727 in Parkinson's Disease Patients

A Prospective, Randomized Placebo Controlled Pilot Study to Characterize the Intestinal Microbiome and to Evaluate the Safety and Fecal Microbiome Changes Following Weekly Administration of Lyophilized PRIM-DJ2727 Given Orally in Subjects With Parkinson's Disease

The purpose of this study is to characterize the intestinal flora in subjects with Parkinson's Disease (PD) and to determine safety and trends in improvements in diversity of colonic microbiome following fecal microbiota transplantation.

Study Overview

• Status: Withdrawn
• Conditions: Parkinson's Disease
• Intervention / Treatment: Biological: PRIM-DJ2727; Drug: Placebo (for PRIM-DJ2727)

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 41 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis PD with a Hoehn and Yahr stage of < 3 in the "Off medicine" state
• Sexually active male and female subjects of child-bearing potential must agree to use an effective method of birth control during the treatment and follow-up period
• Female subjects of child-bearing potential must have a negative pregnancy test in the 72 hours before the procedure
• Subject willing to sign an informed consent form
• Subject deemed likely to survive for ≥ 1 year after enrolment
• Subject's attending physician will refer and provide non-transplant care for the subject
• Subjects must demonstrate adherence to and the ability to maintain a Parkinson's therapy medical regimen that is stable for 90 days before enrolment and participation in the study.

Exclusion Criteria:

• Greater than 20 grams of ethanol intake daily
• Unstable Parkinson's disease
• Other immune disorder or clinical immunosuppression
• Probiotic used during study period
• Severe underlying disease such that the subject is not expected to survive for one or more years or unstable medical condition requiring frequent change in treatments
• Current or recent within one month receipt of an antibiotic with expected activity against enteric bacteria
• Prior Deep Brain Stimulation, or surgical intervention for PD , intravenous glutathione therapy or stem cell therapy
• HIV or Hepatitis B / C positive

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PRIM-DJ2727; Subjects with PD will be randomly assigned to receive PRIM-DJ2727 in orally administered enteric-coated capsules	Biological: PRIM-DJ2727; Thirty eligible subjects with PD will be randomly assigned to receive either PRIM-DJ2727 in orally administered enteric-coated capsules or placebo capsules
Placebo Comparator: Placebo; Thirty eligible subjects with PD will be randomly assigned to receive placebo capsules	Drug: Placebo (for PRIM-DJ2727); Thirty eligible subjects with PD will be randomly assigned to receive placebo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Microbiome Diversity in Fecal Samples s Indicated by the Shannon Diversity Index	3 years
Microbiome Diversity in Fecal Samples s Indicated by the Shannon Diversity Index	6 months
Microbiome Diversity in Fecal Samples s Indicated by the Shannon Diversity Index	12 months
Microbiome Richness in Fecal Samples as Indicated by the Number of Taxonomies per Participant	3 years
Microbiome Richness in Fecal Samples as Indicated by the Number of Taxonomies per Participant	6 months
Microbiome Richness in Fecal Samples as Indicated by the Number of Taxonomies per Participant	12 months
Most abundant Phylum in Fecal Sample	3 years
Most abundant Phylum in Fecal Sample	6 months
Most abundant Phylum in Fecal Sample	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvements in flora diversity by oral administration of a fecal suspension from healthy donors comparing data with untreated controls		3 years
Number of bowel movements per day		3 years
Number of bowel movements per day		6 months
Number of bowel movements per day		12 months
Neurologic functioning as indicated by score on the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	The (MDS-UPDRS) measures mentation, behaviour, mood, activities of daily living and motor manifestations and the Montreal Cognitive Assessment (MoCA) for memory assessment.	3 years
Neurologic functioning as indicated by score on the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	The (MDS-UPDRS) measures mentation, behaviour, mood, activities of daily living and motor manifestations and the Montreal Cognitive Assessment (MoCA) for memory assessment.	1 day
Neurologic functioning as indicated by score on the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	The (MDS-UPDRS) measures mentation, behaviour, mood, activities of daily living and motor manifestations and the Montreal Cognitive Assessment (MoCA) for memory assessment.	6 months
Neurologic functioning as indicated by score on the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	The (MDS-UPDRS) measures mentation, behaviour, mood, activities of daily living and motor manifestations and the Montreal Cognitive Assessment (MoCA) for memory assessment.	12 months
Number of participants with a change in required anti-PD symptomatic or levodopa therapy		12 months
Subject assessment of global improvement in PD and quality of life as indicated by score the self-survey Parkinson's Disease Questionnaire 39 (PDQ-39)		3 years
Subject assessment of global improvement in PD and quality of life as indicated by score the self-survey Parkinson's Disease Questionnaire 39 (PDQ-39)		day 1 of treatment
Subject assessment of global improvement in PD and quality of life as indicated by score the self-survey Parkinson's Disease Questionnaire 39 (PDQ-39)		6 months
Subject assessment of global improvement in PD and quality of life as indicated by score the self-survey Parkinson's Disease Questionnaire 39 (PDQ-39)		12 months
Memory as assessed by score on the Montreal Cognitive Assessment (MoCA)		3 years
Memory as assessed by score on the Montreal Cognitive Assessment (MoCA)		day 1 of treatment
Memory as assessed by score on the Montreal Cognitive Assessment (MoCA)		6 months
Memory as assessed by score on the Montreal Cognitive Assessment (MoCA)		12 months
Number of participants with worsening of PD symptoms or other potential flora-mediated disorders as indicated by patient diares		12 months

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: Kelsey Research Foundation
• Investigators: Principal Investigator: Herbert L DuPont, MD, The University of Texas Health Science Center, Houston

Publications and helpful links

General Publications

• Borody TJ, Paramsothy S, Agrawal G. Fecal microbiota transplantation: indications, methods, evidence, and future directions. Curr Gastroenterol Rep. 2013 Aug;15(8):337. doi: 10.1007/s11894-013-0337-1.
• Fasano A, Bove F, Gabrielli M, Petracca M, Zocco MA, Ragazzoni E, Barbaro F, Piano C, Fortuna S, Tortora A, Di Giacopo R, Campanale M, Gigante G, Lauritano EC, Navarra P, Marconi S, Gasbarrini A, Bentivoglio AR. The role of small intestinal bacterial overgrowth in Parkinson's disease. Mov Disord. 2013 Aug;28(9):1241-9. doi: 10.1002/mds.25522. Epub 2013 May 27.
• Nakane S, Yoshioka M, Oda N, Tani T, Chida K, Suzuki M, Funakawa I, Inukai A, Hasegawa K, Kuroda K, Mizoguchi K, Shioya K, Sonoda Y, Matsuo H. The characteristics of camptocormia in patients with Parkinson's disease: A large cross-sectional multicenter study in Japan. J Neurol Sci. 2015 Nov 15;358(1-2):299-303. doi: 10.1016/j.jns.2015.09.015. Epub 2015 Sep 8.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 15, 2017
• Primary Completion (Actual): July 17, 2018
• Study Completion (Actual): July 17, 2018

Study Registration Dates

• First Submitted: January 11, 2017
• First Submitted That Met QC Criteria: January 17, 2017
• First Posted (Estimate): January 20, 2017

Study Record Updates

• Last Update Posted (Actual): August 10, 2018
• Last Update Submitted That Met QC Criteria: August 8, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Fecal microbiota transplantation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: UT-SPH/KRF FMT-2016-PD-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No