GBPDC: Gut-Brain in PD Consortium Master Protocol (GBPDC)
Consortium for Gut-Brain Communication in Parkinson's Disease Master Protocol
The purpose of this research study is to identify the role that the gut-brain axis, the group of nerves that connect the brain and gut, plays in Parkinson's disease (PD). The National Institute of Diabetes and Digestive and Kidney Diseases is sponsoring this research study.
During this study, specific groups of participants, also known as "cohorts", will be identified based on the severity of their PD. There will also be a cohort enrolling participants who do not have Parkinson's and a cohort enrolling participants that are at risk for developing PD. Each of these cohorts will be compared to the others to assess the differences in the gut-brain connection.
Participants in this study will:
- meet with a medical provider
- answer questionnaires
- give samples of blood, stool, and saliva
- have X-rays taken while swallowing different foods (swallowing study)
- have X-rays taken to see how long it takes markers to move through their colon (colon transit study)
- have a flexible sigmoidoscopy, where a doctor looks inside the lower part of the colon and takes small tissue samples (biopsies) from the mucosa (lining)
- have samples taken of their skin
- have an anorectal manometry and a balloon expulsion test, where a small tube and balloon are placed in the rectum to measure muscle function.
Participation in the study will last up to 24 months (2 years).
Aperçu de l'étude
Statut
Description détaillée
The objectives of the master protocol are to establish a common platform that: (1) assures the collection, integration, and analysis of a set of uniformly collected data across all participating centers, and (2) follows the objective of the Gut-Brain Parkinson's Disease Consortium (GBPDC) with the goal "to enhance our understanding of the temporal onset of GI symptoms in PD and changes in gut-brain communication that can be used to leverage the potential role of the GI tract in the pathogenesis and progression of PD and to improve patient diagnosis, care, and outcomes."
Primary Objective
1. To collect prospective cross-sectional and longitudinal participant biospecimens with temporally coordinated evaluations of GI and neurological symptoms and functions to better characterize the phenotype of people with PD versus those without.
Secondary Objectives
- To elucidate the biological processes and pathways relevant to the role of the GI tract in the pathogenesis and progression of PD.
- To characterize GI symptoms, pathology, and gut-brain communication in PD to detect early and longitudinal changes in gut function and activity that correspond to the development or progression of PD.
Exploratory Objectives
- To identify possible novel gut-based biomarkers (functional, molecular, etc.), diagnostic tools, and therapeutic targets.
- To investigate the impact of neuroimmune interactions and other pathways in the GI tract on gut-brain communication and PD risk.
In conjunction with clinical, social, and environmental characterization, biospecimen collection within the GBPDC master protocol will provide the opportunity to probe and characterize the pathophysiologic underpinnings of the gut-brain axis in PD, refine existing biomarker testing for PD, and identify new biomarkers that could allow early detection of PD or new targets for treatment.
Duke University will serve as the biorepository for the GBPDC. Participants and study site personnel will collect, process, and ship biospecimens according to the GBPDC Biorepository Manual of Procedures using standard kits assembled specifically for the GBPDC master protocol. Biospecimens will be shipped from the study sites to the GBPDC central biorepository at Duke University for accessioning, storage, tracking, and subsequent distribution for use in approved future research. Throughout the conduct of the master protocol, a portion of the biospecimens received by the GBPDC central biorepository will be transferred to the NIDDK biorepository for approved research use. Any biospecimen aliquots remaining at the GBPDC central biorepository at the termination of the GBPDC program will be transferred to the NIDDK biorepository.
Statistical Design This is a prospective, observational, longitudinal cohort study designed to characterize gut-brain communication in Parkinson's Disease. The study employs a longitudinal design, including cross-sectional analyses of baseline data, to evaluate gastrointestinal and neurological functions in participants with PD compared to household controls and a prodromal cohort, as well as comparisons among PD severity subgroups.
Study Design Features:
- Multi-center observational study across 5 GNRCs
- Three participant cohorts: people with PD, people with prodromal features of PD, and household controls. The PD cohort will be further classified as mild, moderate, or severe PD.
- Longitudinal design with assessments at baseline, 6, 12, 18, and 24 months
- Comprehensive biospecimen collection coordinated with clinical assessments
- Household control design where controls are matched to people with PD when available
Type d'étude
Inscription (Estimé)
Contacts et emplacements
Lieux d'étude
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California
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Stanford, California, États-Unis, 94305
- Recrutement
- Stanford University
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Contact:
- Marian Shahid-Besanti, MSc
- Numéro de téléphone: 650-723-0060
- E-mail: gutbrainresearch@stanford.edu
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Chercheur principal:
- Kathleen L Poston, MD, MS
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Chercheur principal:
- Laren S Beckers, MD
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Illinois
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Chicago, Illinois, États-Unis, 60637
- Pas encore de recrutement
- University of Chicago
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Chercheur principal:
- Tao Xie, MD, PhD
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Chercheur principal:
- Eugene Chang, MD
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Contact:
- Hanna Lancerio
- Numéro de téléphone: 773-633-8412
- E-mail: hlancerio@bsd.uchicago.edu
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Chicago, Illinois, États-Unis, 60612
- Recrutement
- Rush University
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Chercheur principal:
- Ali Keshavarzian, MD
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Contact:
- Michelle Villanueva, MS
- Numéro de téléphone: 312-942-8927
- E-mail: michelle_villanueva@rush.edu
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Chercheur principal:
- Christopher Goetz, MD
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Massachusetts
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Boston, Massachusetts, États-Unis, 02114
- Pas encore de recrutement
- Massachusetts General Hospital
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Contact:
- Anna Borodianski
- Numéro de téléphone: 617-724-0480
- E-mail: GIMotilityResearch@MGH.HARVARD.EDU
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Chercheur principal:
- Aleksander Videnovic, MD
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Minnesota
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Rochester, Minnesota, États-Unis, 55905
- Recrutement
- Mayo Clinic
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Chercheur principal:
- Adil Bharucha, MBBS, MD
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Contact:
- Kelly Feuerhak, BSN, RN, CCRP
- Numéro de téléphone: 507-255-6802
- E-mail: rstgistudy@mayo.edu
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Chercheur principal:
- Rodolfo Savica, MD, PhD
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New York
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New York, New York, États-Unis, 10027
- Pas encore de recrutement
- Columbia University
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Chercheur principal:
- Braden Kuo, MD
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Contact:
- Katharine Godfrey
- E-mail: kb3217@cumc.columbia.edu
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South Carolina
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Charleston, South Carolina, États-Unis, 29425
- Pas encore de recrutement
- Medical University of South Carolina
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Contact:
- Stephanie N Slan, MBA, ACRP-CP
- E-mail: slans@musc.edu
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
Méthode d'échantillonnage
Population étudiée
La description
Inclusion Criteria (All PD Cohorts)
- Aged ≥21 years old and ≤80 years old
- Clinical diagnosis of PD as defined by Movement Disorder Society (MDS) PD Criteria
- Adequate visual, hearing, cognitive, and physical ability
- Willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures. Because longitudinal participation is important to the scientific goals of the program, a "best estimate" of interest, commitment, and geographic feasibility for three years will be documented by the enrolling investigator after interview with the potential enrollee
Inclusion Criteria Controls
- Aged ≥21 years old and ≤80 years old
- No known or diagnosed neurodegenerative disease
- Willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures
- Resides within the same household as person with PD
Inclusion Criteria Prodromal Cohort
- Aged ≥21 years old and ≤80 years old
- Prodromal characteristics are defined by the MDS Research Criteria for PD and include either polysomnography (PSG)-confirmed rapid eye movement sleep behavior disorder (RBD) or possible RBD (questionnaire-based), with hyposmia as defined by the University of Pennsylvania Smell Identification Test (UPSIT) ≤ 15th percentile.
Exclusion Criteria (All Cohorts)
- Diagnosis of secondary or atypical parkinsonism
Laboratory Values:
- Hemoglobin (Hgb) <10
- Platelets <70,000
- Alanine Transaminase (ALT) or Aspartate Aminotransferase (AST) > 2 1/2 times upper limit of normal (ULN)
- Moderate or severe renal disease with an estimated glomerular filtration rate (eGFR) <60 mL/min/BSA [body surface area]) calculated using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation, or moderate or severe hepatic impairment (alkaline phosphatase [ALP] >2.0 times the ULN and/or total bilirubin >2.0 times the ULN)
- Significantly above the normal range for PT/INR/PTT
- Currently taking anticoagulants that are deemed exclusionary by the investigator for risk of bleeding with sigmoidoscopy procedure
- Clinically significant cognitive impairment with a Montreal Cognitive Assessment (MOCA) score <22
- Clinical or laboratory findings consistent with another primary neurodegenerative disease or cognitive disorder other than PD, including but not limited to, frontotemporal lobar disease, Huntington's disease, progressive supranuclear palsy, multisystem atrophy, Creutzfeld-Jakob- Disease, Down's syndrome, cortico-basal degeneration, dementia with Lewy Bodies, Alzheimer's disease, amyotrophic lateral sclerosis, seizure disorder, stroke, or other infectious, metabolic, or systemic disease affecting the central nervous system including, but not limited to, syphilis, present hypothyroidism, present or unaddressed/treated vitamin B12 deficiency, or other screening laboratory abnormalities
- Suicidality, defined as active suicidal thoughts or ideation within 6 months before Screening or at Baseline, defined as answering yes to items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS), or history of suicide attempt in previous 2 years, or, in the Investigator's opinion, at serious risk of suicide
- Has cancer or has had a malignant tumor within the past 5 years. (Participants with stable untreated prostate cancer or treated/removed cutaneous carcinomas are not excluded.)
- Any medical condition or systemic disease that, in the Investigator's opinion, may either put the participant at risk because of participation in the study, influence the results or proposed analyses, or impair the participant's ability to fully participate in the study
- Body mass index (BMI) >35 kg/m2 or body weight <50 kg
- Participant is currently pregnant, breastfeeding, and/or lactating
- History of alcohol or substance abuse or dependence within the past 2 years (DSM IV criteria)
- History of Covid 19 (SARS-CoV-2) infection within 6 weeks prior to screening.
- Participants with unresolved symptoms of Covid 19 infection or ongoing cognitive or other deficits attributable to post-Covid 19 that may affect participant safety or interfere with cognitive assessments based on the Investigator's clinical judgment
- Either ongoing or current participation in another clinical trial with an investigational agent and have taken at least one dose of study medication, unless unblinded on placebo, within 4 weeks prior to the start of screening, or five half-lives of the investigational drug, whichever is greater. The end of a previous investigational trial is the date the last dose of an investigational agent was taken. Participation in other research studies (e.g., observational studies) may be acceptable throughout this study.
- History of GI surgery. (However, patients with appendicectomy, hemorrhoid surgery, and cholecystectomy will be eligible to participate).
- Regular use of medication that impacts the intestinal barrier (e.g., NSAID more than 3 times weekly)
- Has a history of Crohn's disease, ulcerative colitis, and/or other types of colitis (microscopic, lymphocytic, or collagenous colitis). Confirmed diagnosis of inflammatory bowel disease (IBD) and/or, active or uncontrolled IBD symptoms such as diarrhea, bleeding, or severe stomach pain. Treatment for IBD in the past 6 months with medicines such as steroids, biologics, or strong immune-suppressing drugs. Surgery to remove part of the bowel due to IBD. Other long-term gut diseases that cause inflammation, such as celiac disease.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
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Household Controls
Age-similar household controls.
Household control design where controls are matched to people with PD when available.
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People with Parkinson's disease
The Parkinson's Disease (PD) cohort will be further classified as mild, moderate, or severe PD as classified by Hoehn and Yahr scale.
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Prodromal Parkinson's disease
People with Parkinson's Disease prodromal features.
Prodromal characteristics are defined by the MDS Research Criteria for PD and include either polysomnography (PSG)-confirmed rapid eye movement sleep behavior disorder (RBD) or possible RBD (questionnaire-based), with hyposmia as defined by the University of Pennsylvania Smell Identification Test (UPSIT) ≤ 15th percentile.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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GI influences on PD
Délai: enrollment to end of observation at 24 months
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Trait and State cross-sectional evaluation of GI influences on PD
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enrollment to end of observation at 24 months
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Co-associations components of the GBA
Délai: enrollment to end of observation at 24 months
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Cross-sectional co-associations components of the GBA
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enrollment to end of observation at 24 months
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Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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GBA Disruption and Parkinson's disease Progression
Délai: enrollment to end of observation at 24 months
|
GBA disruption triggered by microbiota dysbiosis (or another GI component of the GBA) predicts PD progression (both motor and non-motor dysfunction/symptoms including GI over time).
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enrollment to end of observation at 24 months
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GBA Disruption and Prodromal Participants
Délai: enrollment to end of observation at 24 months
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Degree of the "type" or "nature" or "form" of the GBA disruption predict development of PD in prodromal participants over time.
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enrollment to end of observation at 24 months
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Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Lisa Wruck, Duke Clinical Research Institute
Publications et liens utiles
Liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- Pro00115811
- 5U24DK140918-02 (Subvention/contrat des NIH des États-Unis)
- 5U01DK140933-02 (Subvention/contrat des NIH des États-Unis)
- 5U01DK140923-02 (Subvention/contrat des NIH des États-Unis)
- 5U01DK140921-02 (Subvention/contrat des NIH des États-Unis)
- 5U01DK140936-02 (Subvention/contrat des NIH des États-Unis)
- 5U01DK140939-02 (Subvention/contrat des NIH des États-Unis)
Plan pour les données individuelles des participants (IPD)
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Description du régime IPD
Informations sur les médicaments et les dispositifs, documents d'étude
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