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NCT04373564PHASE4Recruiting

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

Guerbet

Start Date

3/24/2021

Completion Date

12/31/2028

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.

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.

Eligibility Criteria

Age Range: 18 years to 64 years

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.

Interventions

PROCEDURE

Motor Tests

PROCEDURE

Cognitive Tests

PROCEDURE

Unenhanced-MRI of the brain

PROCEDURE

Gadolinium Measurements

DRUG

Gadoxetate disodium

DRUG

Gadobenate dimeglumine

DRUG

Gadodiamide

DRUG

Gadoterate meglumine

DRUG

Gadobutrol

DRUG

Gadoteridol

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Conditions

Motor FunctionCognitive FunctionContrast Media

Locations

Scottsdale Medical Imaging, LLC

Scottsdale, Arizona 85260

United States

Yale University School of Medicine

New Haven, Connecticut 06520

United States

University of Chicago Medical Center

Chicago, Illinois 60637

United States

Methodist Medical Center of Illinois

Peoria, Illinois 61637

United States

Massachussets General Hospital

Boston, Massachusetts 02114

United States

Boston University Medical Center

Boston, Massachusetts 02118

United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts 02215

United States

ActivMed Practices & Research, Inc.

Methuen, Massachusetts 01844

United States

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts 01655

United States

Department of Radiology

St Louis, Missouri 63110

United States

UNC School of Medicine

Chapel Hill, North Carolina 27599

United States

Penn State Hershey Medical Center

Hershey, Pennsylvania 17033

United States

Albert Einstein Healthcare Network

Philadelphia, Pennsylvania 19141

United States

UT Southwestern Medical Center

Dallas, Texas 75390

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

University of Wisconsin

Madison, Wisconsin 53792

United States

Hospital Santa Marta

Taguatinga, Federal District 72025-110

Brazil

Liga Norte-Rio-Grandense Contra o Câncer

Natal, Rio Grande do Norte 59075-740

Brazil

Instituto Mederi de Pesquisa e Saude

Passo Fundo, Rio Grande do Sul 99010-120

Brazil

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul 90035-001

Brazil

Instituto Baía Sul de Ensino e Pesquisa (IEP)

Florianópolis, Santa Catarina 88020-210

Brazil

CEMEC - Oncológica

São Bernardo do Campo, São Paulo 09715-090

Brazil

Fundação Faculdade Regional de Medicina de São José do Rio Preto

São José do Rio Preto, São Paulo 15090-000

Brazil

CPCLIN - Centro de Pesquisas Clínicas Ltda.

São Paulo, São Paulo 01228-200

Brazil

Albert Einstein Sociedade Beneficente Israelita Brasileira

São Paulo, São Paulo 05652000

Brazil

CEMEC - Oncológica

São Bernardo do Campo,

Brazil

G. Kenneth Jansz Medical Professional Corporation

Burlington, Ontario L7N 3V2

Canada

Groupe Hospitalier Pitie-Salpetriere

Paris, 75013

France

CHU Strasbourg - Hôpital Hautepierre

Strasbourg, 67200

France

Universitaetsklinikum Tuebingen

Tübingen, Baden-Wurttemberg 72076

Germany

Vivantes Klinikum Neukoelln

Berlin, 12351

Germany

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

Siena, Siena 53100

Italy

Azienda Ospedaliera Universitaria di Trieste

Trieste, Trieste 34125

Italy

Ospedale San Raffaele

Milan, 20123

Italy

Università Campus Bio-Medico di Roma

Roma, 00128

Italy

Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)

Verona, 37134

Italy

BHI of Omsk region "Clinical Oncology Dispensary"

Omsk, 644013

Russia

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

Saint Petersburg, 192019

Russia

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

Saint Petersburg, 197341

Russia

LLC Medical Center Mart

Saint Petersburg, 199178

Russia

RSBIH "Smolensk Regional Clinical Hospital"

Smolensk, 214019

Russia

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

Tomsk, 634009

Russia

SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan

Ufa, 450054

Russia

Hallym University Chuncheon Sacred Heart Hospital

Chuncheon, Gangwon-do 24253

South Korea

Chonnam National University Hospital

Gwangju, Gyeonggi-do 61469

South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do 13620

South Korea

Inje University Busan Paik Hospital

Busan, 47392

South Korea

Pusan National University Hospital

Busan, 49241

South Korea

Chosun University Hospital

Gwangju, 61453

South Korea

Gangnam Severance Hospital, Yonsei University Health System

Seoul, 06273

South Korea

Chung-Ang University Hospital

Seoul, 06973

South Korea