Effect on Body Movement and Mental Skills in Patients Who Received Gadolinium-based Contrast Media for Magnetic Resonance Examination Multiple Times Within 5 Years (ODYSSEY)

January 8, 2023 updated by: Guerbet

Prospective Evaluation of Potential Effects of Repeated Gadolinium-based Contrast Agent (GBCA) Administrations of the Same GBCA on Motor and Cognitive Functions in Neurologically Normal Adults in Comparison to a Non-GBCA Exposed Control Group

This study is a postmarketing requirement jointly carried out by four NDA holders (Bayer AG, Bracco, GE Healthcare and Guerbet) and the CRO IQVIA.

The study aims to create detailed images of the organs and tissue of the human body during x-ray, CT-scan or MRI investigations, doctors are using contrast media (a kind of dye) which can be given to patients by injection into a blood vessel or by mouth.

In this study researchers want to find out whether so called gadolinium-based contrast agents (GBCAs) have an effect on body movement and mental skills when given to participants multiple times within 5 years.

The study plans to enroll about 2076 participants suffering from a condition for which they are likely to have at least annually a MRI or another imaging examinations. Only adults up to 65 years will be considered to join this study. During the study duration of 5 years participants will receive annually a MRI or other imaging tests (such as CT-scan, x-ray) and will visit the study doctor at least 7 times for physical examinations, laboratory investigations and tests on body movement and mental skills.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The primary objective of the study is to assess the potential effect of repeated exposure to either a linear or a macrocyclic gadolinium-based contrast agent (GBCA) on change from baseline to Year 5 in composite measure of motor and cognitive function among neurologically normal adults in comparison to a matched non-GBCA- exposed control group.

The secondary objectives comprise the assessment of the following endpoints in GBCA-exposed participants as compared to controls a) changes from baseline in composite measure of motor and cognitive function post-baseline on yearly basis (Years 1 to 4); b) changes from baseline in each individual test of motor and cognitive function on yearly basis (Years 1 to 5). Total Gd concentrations in blood and urine samples on yearly basis (Years 1 to 5) and adverse events will be collected as secondary objectives.

Of note : The study is considered interventional because of the addition of UE-MRI scans for all participants, as well as blood sampling and the administration of the motor and cognitive tests. The GBCA administered as part of the contrast-enhanced MR imaging in the experimental arms is not the intervention in this study. Neither the protocol nor the investigators assign patients to a specific GBCA as part of the study, making this part of the study observational rather than interventional. The participants were already scheduled, prior to study screening, to undergo CE-MRI as part of their clinical care. The choice of GBCA for the CE-MRI will be based on medical need and institutional usage of GBCA, independent of study participation.

Study Type

Interventional

Enrollment (Anticipated)

2076

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Brazil
      • Sao Bernardo Do Campo, Brazil
        • Not yet recruiting
        • CEMEC - Oncológica
        • Contact:
        • Principal Investigator:
          • Luis Eduardo Werneck de Carvalho, MD
    • Distrito Federal
      • Taguatinga, Distrito Federal, Brazil, 72025-110
    • RS
      • Passo Fundo, RS, Brazil, 99010-120
        • Recruiting
        • Instituto Mederi de Pesquisa E Saude
        • Contact:
        • Principal Investigator:
          • Cassiano Mateus Forcelini, MD
      • Porto Alegre, RS, Brazil, 90035-001
        • Recruiting
        • Hospital Moinhos de Vento
        • Contact:
        • Principal Investigator:
          • Guilherme Hohgraefe Neto, MD
    • Rio Grande Do Norte
      • Natal, Rio Grande Do Norte, Brazil, 59075-740
        • Recruiting
        • Liga Norte-Rio-Grandense Contra o Cancer
        • Contact:
        • Principal Investigator:
          • Rita de Cassia Simoes Matheus, MD
    • SP
      • São José Do Rio Preto, SP, Brazil, 15090-000
        • Recruiting
        • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
        • Contact:
        • Principal Investigator:
          • Kathia Abdalla
      • São Paulo, SP, Brazil, 01228-200
        • Recruiting
        • CPCLIN - Centro de Pesquisas Clínicas Ltda.
        • Contact:
          • Study Coordinator
          • Phone Number: +551127110253
        • Principal Investigator:
          • Lis Gomes, MD
    • Santa Catarina
      • Florianopolis, Santa Catarina, Brazil, 88020-210
        • Recruiting
        • Instituto Baía Sul de Ensino e Pesquisa (IEP)
        • Contact:
        • Principal Investigator:
          • Israel Silva Maia, MD
    • Sao Paulo
      • São Bernardo do Campo, Sao Paulo, Brazil, 09715-090
  • Canada
    • Ontario
      • Burlington, Ontario, Canada, L7N 3V2
        • Withdrawn
        • G. Kenneth Jansz Medical Professional Corporation
  • Italy
      • Siena, Italy, 53100
        • Recruiting
        • A.O.U. Senese Policlinico Santa Maria alle Scotte
        • Principal Investigator:
          • Alfonso Cerase, MD
      • Trieste, Italy, 34125
        • Recruiting
        • Azienda Ospedaliera Universitaria di Trieste
        • Contact:
        • Principal Investigator:
          • Alessandra Guglielmi, MD
  • Korea, Republic of
      • Busan, Korea, Republic of, 49241
        • Recruiting
        • Pusan National University Hospital
        • Principal Investigator:
          • Jeong Heo, MD
        • Contact:
      • Busan, Korea, Republic of, 47392
        • Recruiting
        • Inje University Busan Paik Hospital
        • Contact:
        • Principal Investigator:
          • Hae Woong Jeong, MD
      • Gwangju, Korea, Republic of, 61453
        • Recruiting
        • Chosun University Hospital
        • Contact:
        • Principal Investigator:
          • JuYeon Cho,, MD
      • Seoul, Korea, Republic of, 06973
        • Recruiting
        • Chung-Ang University Hospital
        • Contact:
        • Principal Investigator:
          • Chang-hwan Choi, MD
      • Seoul, Korea, Republic of, 06273
        • Recruiting
        • Gangnam Severance Hospital, Yonsei University Health System
        • Contact:
        • Principal Investigator:
          • Joon Jeong, MD
    • Gangwon-do
      • Chuncheon, Gangwon-do, Korea, Republic of, 24253
        • Recruiting
        • Hallym University Chuncheon Sacred Heart Hospital
        • Contact:
        • Principal Investigator:
          • Dong Joon Kim, MD
    • Gyeonggi-do
      • Gwangju, Gyeonggi-do, Korea, Republic of, 61469
        • Recruiting
        • Chonnam National University Hospital
        • Contact:
        • Principal Investigator:
          • Sang Soo Shin, MD
      • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
        • Recruiting
        • Seoul National University Bundang Hospital
        • Contact:
        • Principal Investigator:
          • Won Chang, MD
  • Russian Federation
      • Omsk, Russian Federation, 644013
        • Suspended
        • BHI of Omsk region "Clinical oncology dispensary"
      • Saint-Petersburg, Russian Federation, 192019
        • Suspended
        • FSBI "National medical scientific center of psychiatry and neurology n.a. V.M. Bekhterev" Adolescent
      • Saint-Petersburg, Russian Federation, 197341
        • Suspended
        • FSBI North-West Federal Medical Research Center n.a. V.A. Almazov of MoH RF
      • Saint-Petersburg, Russian Federation, 199178
        • Suspended
        • LLC Medical Center Mart
      • Smolensk, Russian Federation, 214019
        • Suspended
        • RSBIH "Smolensk Regional Clinical Hospital"
      • Tomsk, Russian Federation, 634009
        • Suspended
        • Federal State Budgetary Scientific Institution "Tomsk National Research Medical Centre of the Russia
      • Ufa, Russian Federation, 450054
        • Suspended
        • SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85260
        • Recruiting
        • Scottsdale Medical Imaging, LLC
        • Principal Investigator:
          • Ronald Korn, MD
        • Contact:
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Withdrawn
        • Yale University School of Medicine
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Medical Center
        • Contact:
        • Principal Investigator:
          • Carla Harmath, MD
      • Peoria, Illinois, United States, 61637
        • Recruiting
        • Methodist Medical Center of Illinois
        • Contact:
        • Principal Investigator:
          • Praveen Sudhindra, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Beth Israel Deaconess Medical Center
        • Contact:
        • Principal Investigator:
          • Leo Tsai, MD
      • Boston, Massachusetts, United States, 02118
        • Recruiting
        • Boston University Medical Center
        • Contact:
          • Phone Number: 617-414-9729
        • Principal Investigator:
          • Fishman Michael, MD
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachussets General Hospital
        • Contact:
          • Phone Number: 617-726-8396
        • Principal Investigator:
          • Mukesh Harisinghani, MD
      • Methuen, Massachusetts, United States, 01844
        • Recruiting
        • ActivMed Practices & Research, Inc.
        • Principal Investigator:
          • Ricardo Sanchez, MD
      • Worcester, Massachusetts, United States, 01655
        • Recruiting
        • University of Massachusetts Memorial Medical Center
        • Contact:
        • Principal Investigator:
          • Boris Nicolas Bloch, MD
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Withdrawn
        • Department of Radiology
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • UNC School of Medicine
        • Contact:
        • Principal Investigator:
          • Lauren Burke, MD
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
      • Philadelphia, Pennsylvania, United States, 19141
        • Recruiting
        • Albert Einstein Healthcare Network
        • Contact:
        • Principal Investigator:
          • Ryan Lee, MD
    • Texas
      • Dallas, Texas, United States, 75390
      • Houston, Texas, United States, 77030
        • Not yet recruiting
        • MD Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • Khaled Elsayes, MD
    • Wisconsin
      • Madison, Wisconsin, United States, 53792

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 64 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Participant must be neurologically normal, defined as free of unstable neurologic and psychiatric disease as confirmed by a normal neurologic examination at screening
  • Participant (GBCA-exposed or controls) agrees to undergo unenhanced magnetic resonance imaging (UE-MRI) of the brain at enrollment and at the end of the observation period (5 years)
  • Participants should have at least 1 of the following indications: a) Medium to high risk for breast cancer or dense breasts undergoing breast cancer screening with MRI, b) Elevated prostate-specific antigen (PSA) and under active diagnostic surveillance for prostate cancer, c) Chronic liver disease (eg, liver cirrhosis limited to Child class A, post-hepatitis chronic hepatopathy, or primary sclerosing cholangitis) for surveillance of hepatocellular carcinoma development, d) Low-grade colorectal cancer or neuroendocrine tumor undergoing screening for liver metastases or e) Branch-duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas (maximum size ≤2 cm) undergoing imaging surveillance.

In addition, for participants in the GBCA Arms only:

  • Each participant should be likely to undergo ≥5 GBCA-enhanced MR examinations with the same GBCA at least annually throughout the 5-year study duration
  • Prospective participants with up to 3 well documented GBCA administrations prior to study screening are acceptable, provided that the imaging was performed with the same GBCA as the one to be prospectively used in the study. If the GBCA used cannot be identified, he/she cannot be enrolled.

For the Control Arm:

  • Participants who never had and are not likely to receive any GBCA injection during the course of the study
  • Each control participant must be willing to undergo UE-MRI of the brain at baseline and at Year 5. In Years 1 to 4, the control participants will undergo their clinically indicated UE-MRIs, computed tomography (CT), ultrasound, or X-ray procedures

Exclusion Criteria:

  • As evidenced by history or determined in the neurologic exam at screening, concurrent neurological and/or psychiatric disease (or treatments) that could influence the results of the study's motor and cognitive tests (e.g. Cerebrovascular disease, Multiple sclerosis, Neurodegenerative disease, Malignant disease other than listed in indications, Carcinoid tumors, Epilepsy, Prior neurosurgery, Psychotic disorders or any prior psychotic episode not otherwise specified - any documented prior history of chronic schizophrenia, Remittent or current medically confirmed major depressive disorder or bipolar disorder, History of long-term major depression or bipolar affective disorder with an active episode in the past 2 to 5 years, Neurodevelopmental disorders (eg, trisomy 21), Uncontrolled severe migraine, Uncontrolled or controlled anxiety or depression within 6 months before enrollment, Screening scores of ≤24 on the MMSE and/or ≥11 on the Hospital Anxiety and Depression Scale (HADS)).
  • Prior, planned, or ongoing chemotherapy or brain irradiation
  • Use of concomitant medication(s) affecting neuro-cognitive or motor function
  • Substance or alcohol abuse as determined by the investigator
  • Alcoholic cirrhosis
  • Renal disease, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2
  • History of environmental/occupational/other exposure to one or more chemicals that may affect cognitive and/or motor function, including, but not limited to, heavy metals (arsenic [As], cadmium [Cd], lead [Pb], manganese [Mn], and mercury [Hg]), pesticides, solvents, or carbon monoxide.
  • Clinical indications requiring >1 contrast enhanced magnetic resonance imaging (CE-MRI) every 6 months
  • Pregnant or nursing (lactating) women
  • Presence of any metal-containing joint implants/prostheses

In addition, for participants in either of the GBCA Arms only:

- Receipt of a GBCA or generic prior to study entry other than the specific GBCA to be administered during the course of the study.

For participants in the Control Arm only:

  • Participants with any previous exposure to a GBCA.
  • Participants with any contraindication to UE-MRI examinations.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Linear GBCAs
Adult participants, who were scheduled for repeated enhanced magnetic resonance imaging (MRI), receive a linear gadoliniumbased contrast agent (GBCA, i.e. Eovist/ Primovist, MultiHance or Omniscan) prior to MRI. Each participant will receive the same GBCA throughout the study.
Procedure: Motor Tests
To assess motor function annually
Procedure: Cognitive Tests
To assess cognitive function annually
Procedure: Unenhanced-MRI of the brain
The UE-MRI of the brain will be performed at baseline and at the year 5 visit in order to exclude presence of a significant MRI abnormality
Procedure: Gadolinium Measurements
Blood samples and spontaneous urine specimens will be collected through the course of the study to measure Gd concentration
Drug: Gadoxetate disodium
Administered as defined by the treating physician as part of routine clinical practice
Other Names:
  • Primovist
  • Eovist
  • BAY86-4873
Drug: Gadobenate dimeglumine
Administered as defined by the treating physician as part of routine clinical practice
Other Names:
  • MultiHance
Drug: Gadodiamide
Administered as defined by the treating physician as part of routine clinical practice
Other Names:
  • Omniscan
Experimental: Macrocyclic GBCAs
Adult participants, who were scheduled for repeated enhanced magnetic resonance imaging (MRI), receive a macrocyclic gadolinium-based contrast agent (GBCA, i.e. Gadavist/ Gadovist, Dotarem, Magnescope or ProHance) prior to MRI. Each participant will receive the same GBCA throughout the study.
Procedure: Motor Tests
To assess motor function annually
Procedure: Cognitive Tests
To assess cognitive function annually
Procedure: Unenhanced-MRI of the brain
The UE-MRI of the brain will be performed at baseline and at the year 5 visit in order to exclude presence of a significant MRI abnormality
Procedure: Gadolinium Measurements
Blood samples and spontaneous urine specimens will be collected through the course of the study to measure Gd concentration
Drug: Gadoterate meglumine
Administered as defined by the treating physician as part of routine clinical practice
Other Names:
  • Dotarem
  • Magnescope
Drug: Gadobutrol
Administered as defined by the treating physician as part of routine clinical practice
Other Names:
  • BAY86-4875
  • Gadavist
  • Gadovist
Drug: Gadoteridol
Administered as defined by the treating physician as part of routine clinical practice
Other Names:
  • ProHance
Other: No GBCA (Control arm)
Adult participants who were never exposed to any gadolinium-based contrast agent and matching the population characteristics of the two GBCA arms. They will not receive any gadolinium-based contrast agent over the study course, but may undergo clinically indicated imaging (e.g. unenhanced magnetic resonance imaging (MRI), unenhanced or enhanced computed tomography, ultrasound and/or X-ray).
Procedure: Motor Tests
To assess motor function annually
Procedure: Cognitive Tests
To assess cognitive function annually
Procedure: Unenhanced-MRI of the brain
The UE-MRI of the brain will be performed at baseline and at the year 5 visit in order to exclude presence of a significant MRI abnormality
Procedure: Gadolinium Measurements
Blood samples and spontaneous urine specimens will be collected through the course of the study to measure Gd concentration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of motor function from baseline to year 5 in comparison to a matched non-GBCA-exposed control group
Time Frame: At baseline, year 5
The endpoint is a composite z score, defined as the weighted sum of the z scores of the individual tests
At baseline, year 5
Change in cognitive function from baseline to year 5 in comparison to a matched non-GBCA-exposed control group
Time Frame: At baseline, year 5
The endpoint is a composite z score, defined as the weighted sum of the z scores of the individual tests
At baseline, year 5

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in the composite endpoints (motor and cognitive) at each of the post-baseline time points (Years 1 to 4) in GBCA-exposed participants as compared to controls.
Time Frame: At baseline, years 1, 2, 3, 4
The endpoint is a composite z score, defined as the weighted sum of the z scores of the individual tests
At baseline, years 1, 2, 3, 4
Change from baseline for each of the individual tests (motor and cognitive) at each of the post-baseline time points (Years 1 to 5) in GBCA-exposed participants as compared to controls.
Time Frame: At baseline, years 1, 2, 3, 4
The endpoint is a composite z score, defined as the weighted sum of the z scores of the individual tests
At baseline, years 1, 2, 3, 4
Number of participants with adverse events
Time Frame: At baseline, years 1, 2, 3, 4, 5
At baseline, years 1, 2, 3, 4, 5
Total Gd concentrations (as measured in a central laboratory) in blood and urine samples taken from exposed and control participants at the time of the annual visit
Time Frame: At baseline, years 1, 2, 3, 4, 5
At baseline, years 1, 2, 3, 4, 5

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Guerbet

Collaborators

Bayer AG (Sponsor)
Bracco (Sponsor)
GEHC (Sponsor)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 24, 2021

Primary Completion (Anticipated)

December 31, 2028

Study Completion (Anticipated)

December 31, 2028

Study Registration Dates

First Submitted

April 30, 2020

First Submitted That Met QC Criteria

April 30, 2020

First Posted (Actual)

May 4, 2020

Study Record Updates

Last Update Posted (Estimate)

January 10, 2023

Last Update Submitted That Met QC Criteria

January 8, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DGD-44-065
  • 20405 (Bayer)
  • GMRA-105 (Other Identifier: Bracco)
  • GE-041-081 (Other Identifier: GE Healthcare)
  • IQVIA-ODYS-001-LZA45541 (Other Identifier: IQVIA)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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