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

NCT04373564 | Recruiting Phase 4 DMC FDA Drug

• 5 other identifiers: DGD-44-06520405GMRA-105GE-041-081IQVIA-ODYS-001-LZA45541
• Study Type: interventional
• Target: 2,076
• Locations: 8 countries
• Sites: 51

Brief Summary

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.

Conditions

Motor Function; Cognitive Function; Contrast Media

Keywords

Motor function assessment; Cognitive function assessment; Magnetic Resonance Imaging (MRI); Gadolinium; Gadolinium-based contrast agent (GBCA); Gadolinium retention; Breast cancer; Prostate cancer; Hepatocellular carcinoma; Colorectal cancer; Neuroendocrine tumor; Branch-duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas

Outcome Measures

Primary Outcomes (2)

• Change of motor function from baseline to year 5 in comparison to a matched non-GBCA-exposed control group

  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

  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 Outcomes (4)

• 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.

  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.

  At baseline, years 1, 2, 3, 4

• Number of participants with adverse events

  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

  At baseline, years 1, 2, 3, 4, 5

Study Arms (3)

Linear GBCAs

EXPERIMENTAL

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; Procedure: Cognitive Tests; Procedure: Unenhanced-MRI of the brain; Procedure: Gadolinium Measurements; Drug: Gadoxetate disodium; Drug: Gadobenate dimeglumine; Drug: Gadodiamide

Macrocyclic GBCAs

EXPERIMENTAL

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; Procedure: Cognitive Tests; Procedure: Unenhanced-MRI of the brain; Procedure: Gadolinium Measurements; Drug: Gadoterate meglumine; Drug: Gadobutrol; Drug: Gadoteridol

No GBCA (Control arm)

OTHER

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; Procedure: Cognitive Tests; Procedure: Unenhanced-MRI of the brain; Procedure: Gadolinium Measurements

Interventions

Motor Tests PROCEDURE

To assess motor function annually

Linear GBCAs; Macrocyclic GBCAs; No GBCA (Control arm)

Cognitive Tests PROCEDURE

To assess cognitive function annually

Linear GBCAs; Macrocyclic GBCAs; No GBCA (Control arm)

Unenhanced-MRI of the brain PROCEDURE

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

Linear GBCAs; Macrocyclic GBCAs; No GBCA (Control arm)

Gadolinium Measurements PROCEDURE

Blood samples and spontaneous urine specimens will be collected through the course of the study to measure Gd concentration

Linear GBCAs; Macrocyclic GBCAs; No GBCA (Control arm)

Gadoxetate disodium DRUG

Administered as defined by the treating physician as part of routine clinical practice

Also known as: Eovist, Primovist, BAY86-4873

Linear GBCAs

Gadobenate dimeglumine DRUG

Administered as defined by the treating physician as part of routine clinical practice

Also known as: MultiHance

Linear GBCAs

Gadodiamide DRUG

Administered as defined by the treating physician as part of routine clinical practice

Also known as: Omniscan

Linear GBCAs

Gadoterate meglumine DRUG

Administered as defined by the treating physician as part of routine clinical practice

Also known as: Dotarem, Magnescope

Macrocyclic GBCAs

Gadobutrol DRUG

Administered as defined by the treating physician as part of routine clinical practice

Also known as: BAY86-4875, Gadavist, Gadovist

Macrocyclic GBCAs

Gadoteridol DRUG

Administered as defined by the treating physician as part of routine clinical practice

Also known as: ProHance

Macrocyclic GBCAs

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Guerbet: lead
• Bayer AG (Sponsor): collaborator
• Bracco (Sponsor): collaborator
• GEHC (Sponsor): collaborator

Study Sites (51)

Scottsdale Medical Imaging, LLC

Scottsdale, Arizona, 85260, United States

RECRUITING

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

WITHDRAWN

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

Methodist Medical Center of Illinois

Peoria, Illinois, 61637, United States

RECRUITING

Massachussets General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Boston University Medical Center

Boston, Massachusetts, 02118, United States

TERMINATED

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

WITHDRAWN

ActivMed Practices & Research, Inc.

Methuen, Massachusetts, 01844, United States

WITHDRAWN

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01655, United States

TERMINATED

Department of Radiology

St Louis, Missouri, 63110, United States

WITHDRAWN

UNC School of Medicine

Chapel Hill, North Carolina, 27599, United States

WITHDRAWN

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

RECRUITING

Albert Einstein Healthcare Network

Philadelphia, Pennsylvania, 19141, United States

RECRUITING

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

WITHDRAWN

University of Wisconsin

Madison, Wisconsin, 53792, United States

RECRUITING

Hospital Santa Marta

Taguatinga, Federal District, 72025-110, Brazil

TERMINATED

Liga Norte-Rio-Grandense Contra o Câncer

Natal, Rio Grande do Norte, 59075-740, Brazil

WITHDRAWN

Instituto Mederi de Pesquisa e Saude

Passo Fundo, Rio Grande do Sul, 99010-120, Brazil

RECRUITING

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, 90035-001, Brazil

RECRUITING

Instituto Baía Sul de Ensino e Pesquisa (IEP)

Florianópolis, Santa Catarina, 88020-210, Brazil

WITHDRAWN

CEMEC - Oncológica

São Bernardo do Campo, São Paulo, 09715-090, Brazil

WITHDRAWN

Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, São Paulo, 15090-000, Brazil

RECRUITING

CPCLIN - Centro de Pesquisas Clínicas Ltda.

São Paulo, São Paulo, 01228-200, Brazil

TERMINATED

Albert Einstein Sociedade Beneficente Israelita Brasileira

São Paulo, São Paulo, 05652000, Brazil

RECRUITING

CEMEC - Oncológica

São Bernardo do Campo, Brazil

WITHDRAWN

G. Kenneth Jansz Medical Professional Corporation

Burlington, Ontario, L7N 3V2, Canada

WITHDRAWN

Groupe Hospitalier Pitie-Salpetriere

Paris, 75013, France

WITHDRAWN

CHU Strasbourg - Hôpital Hautepierre

Strasbourg, 67200, France

RECRUITING

Universitaetsklinikum Tuebingen

Tübingen, Baden-Wurttemberg, 72076, Germany

ACTIVE NOT RECRUITING

Vivantes Klinikum Neukoelln

Berlin, 12351, Germany

RECRUITING

A.O.U. Senese Policlinico Santa Maria alle Scotte

Siena, Siena, 53100, Italy

RECRUITING

Azienda Ospedaliera Universitaria di Trieste

Trieste, Trieste, 34125, Italy

RECRUITING

Ospedale San Raffaele

Milan, 20123, Italy

RECRUITING

Università Campus Bio-Medico di Roma

Roma, 00128, Italy

RECRUITING

Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)

Verona, 37134, Italy

RECRUITING

BHI of Omsk region "Clinical Oncology Dispensary"

Omsk, 644013, Russia

SUSPENDED

FSBI "National medical scientific center of psychiatry and neurology n.a. V.M. Bekhterev" Adolescent

Saint Petersburg, 192019, Russia

SUSPENDED

FSBI North-West Federal Medical Research Center n.a. V.A. Almazov of MoH RF

Saint Petersburg, 197341, Russia

SUSPENDED

LLC Medical Center Mart

Saint Petersburg, 199178, Russia

SUSPENDED

RSBIH "Smolensk Regional Clinical Hospital"

Smolensk, 214019, Russia

SUSPENDED

Federal State Budgetary Scientific Institution "Tomsk National Research Medical Centre of the Russia

Tomsk, 634009, Russia

SUSPENDED

SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan

Ufa, 450054, Russia

SUSPENDED

Hallym University Chuncheon Sacred Heart Hospital

Chuncheon, Gangwon-do, 24253, South Korea

WITHDRAWN

Chonnam National University Hospital

Gwangju, Gyeonggi-do, 61469, South Korea

WITHDRAWN

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

RECRUITING

Inje University Busan Paik Hospital

Busan, 47392, South Korea

RECRUITING

Pusan National University Hospital

Busan, 49241, South Korea

RECRUITING

Chosun University Hospital

Gwangju, 61453, South Korea

RECRUITING

Gangnam Severance Hospital, Yonsei University Health System

Seoul, 06273, South Korea

RECRUITING

Chung-Ang University Hospital

Seoul, 06973, South Korea

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Prostatic Neoplasms; Carcinoma, Hepatocellular; Colorectal Neoplasms; Neuroendocrine Tumors

Interventions

Neuropsychological Tests; gadolinium ethoxybenzyl DTPA; gadobenic acid; gadodiamide; gadoterate meglumine; gadobutrol; gadoteridol

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Psychological Tests; Behavioral Disciplines and Activities

Central Study Contacts

Nathalie LE FUR, PhD

CONTACT

+33649351166; nathalie.lefur@guerbet.com

Frantz HEBERT

CONTACT

+33680249334; frantz.hebert@guerbet.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2020
• First Posted: May 4, 2020
• Study Start: March 24, 2021
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

RU (7); FR (2); IT (5); CA (1); DE (2); BR (10); US (16); KR (8)