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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04373564
Other study ID # DGD-44-065
Secondary ID 20405GMRA-105GE-
Status Recruiting
Phase Phase 4
First received
Last updated
Start date March 24, 2021
Est. completion date December 31, 2028

Study information

Verified date May 2024
Source Guerbet
Contact Nathalie LE FUR, PhD
Phone +33649351166
Email nathalie.lefur@guerbet.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 2076
Est. completion date December 31, 2028
Est. primary completion date December 31, 2028
Accepts healthy volunteers No
Gender All
Age group 18 Years to 64 Years
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

Procedure:
Motor Tests
To assess motor function annually
Cognitive Tests
To assess cognitive function annually
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
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
Gadobenate dimeglumine
Administered as defined by the treating physician as part of routine clinical practice
Gadodiamide
Administered as defined by the treating physician as part of routine clinical practice
Gadoterate meglumine
Administered as defined by the treating physician as part of routine clinical practice
Gadobutrol
Administered as defined by the treating physician as part of routine clinical practice
Gadoteridol
Administered as defined by the treating physician as part of routine clinical practice

Locations

Country Name City State
Brazil Instituto Baía Sul de Ensino e Pesquisa (IEP) Florianopolis Santa Catarina
Brazil Liga Norte-Rio-Grandense Contra o Câncer Natal Rio Grande Do Norte
Brazil Instituto Mederi de Pesquisa e Saude Passo Fundo RS
Brazil Hospital Moinhos de Vento Porto Alegre RS
Brazil CEMEC - Oncológica Sao Bernardo Do Campo
Brazil CEMEC - Oncológica São Bernardo do Campo Sao Paulo
Brazil Fundação Faculdade Regional de Medicina de São José do Rio Preto São José Do Rio Preto SP
Brazil Albert Einstein Sociedade Beneficente Israelita Brasileira São Paulo SP
Brazil CPCLIN - Centro de Pesquisas Clínicas Ltda. São Paulo SP
Brazil Hospital Santa Marta Taguatinga Distrito Federal
Canada G. Kenneth Jansz Medical Professional Corporation Burlington Ontario
France Groupe Hospitalier Pitie-Salpetriere Paris
France CHU Strasbourg - Hôpital Hautepierre Strasbourg
Germany Universitaetsklinikum Tuebingen Tuebingen Baden Wuerttemberg
Italy A.O.U. Senese Policlinico Santa Maria alle Scotte Siena
Italy Azienda Ospedaliera Universitaria di Trieste Trieste
Korea, Republic of Inje University Busan Paik Hospital Busan
Korea, Republic of Pusan National University Hospital Busan
Korea, Republic of Hallym University Chuncheon Sacred Heart Hospital Chuncheon Gangwon-do
Korea, Republic of Chonnam National University Hospital Gwangju Gyeonggi-do
Korea, Republic of Chosun University Hospital Gwangju
Korea, Republic of Seoul National University Bundang Hospital Seongnam-si Gyeonggi-do
Korea, Republic of Chung-Ang University Hospital Seoul
Korea, Republic of Gangnam Severance Hospital, Yonsei University Health System Seoul
Russian Federation BHI of Omsk region "Clinical Oncology Dispensary" Omsk
Russian Federation FSBI "National medical scientific center of psychiatry and neurology n.a. V.M. Bekhterev" Adolescent Saint-Petersburg
Russian Federation FSBI North-West Federal Medical Research Center n.a. V.A. Almazov of MoH RF Saint-Petersburg
Russian Federation LLC Medical Center Mart Saint-Petersburg
Russian Federation RSBIH "Smolensk Regional Clinical Hospital" Smolensk
Russian Federation Federal State Budgetary Scientific Institution "Tomsk National Research Medical Centre of the Russia Tomsk
Russian Federation SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan Ufa
United States Beth Israel Deaconess Medical Center Boston Massachusetts
United States Boston University Medical Center Boston Massachusetts
United States Massachussets General Hospital Boston Massachusetts
United States UNC School of Medicine Chapel Hill North Carolina
United States University of Chicago Medical Center Chicago Illinois
United States UT Southwestern Medical Center Dallas Texas
United States Penn State Hershey Medical Center Hershey Pennsylvania
United States MD Anderson Cancer Center Houston Texas
United States University of Wisconsin Madison Wisconsin
United States ActivMed Practices & Research, Inc. Methuen Massachusetts
United States Yale University School of Medicine New Haven Connecticut
United States Methodist Medical Center of Illinois Peoria Illinois
United States Albert Einstein Healthcare Network Philadelphia Pennsylvania
United States Department of Radiology Saint Louis Missouri
United States Scottsdale Medical Imaging, LLC Scottsdale Arizona
United States University of Massachusetts Memorial Medical Center Worcester Massachusetts

Sponsors (4)

Lead Sponsor Collaborator
Guerbet Bayer AG (Sponsor), Bracco (Sponsor), GEHC (Sponsor)

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  France,  Germany,  Italy,  Korea, Republic of,  Russian Federation, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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 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. 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
Secondary 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. 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
Secondary Number of participants with adverse events At baseline, years 1, 2, 3, 4, 5
Secondary 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
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