Recruiting

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

Sponsor:

Guerbet

Code:

NCT04373564

Conditions

Motor Function

Cognitive Function

Contrast Media

Eligibility Criteria

Sex: All

Age: 18 - 64

Healthy Volunteers: Not accepted

Interventions

Motor Tests

Cognitive Tests

Unenhanced-MRI of the brain

Gadolinium Measurements

Gadoxetate disodium

Study Details

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

Study ID

NCT04373564

Start date

Mar 24, 2021

Status verified date

Jan, 2026

Completion date

Dec 31, 2028

Anticipated

Primary completion date

Dec 31, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 64

Healthy Volunteers: Not accepted

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

Enrollment

2076 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Other

Interventions and Outcome Measures

Arms

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.

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.

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).

Interventions

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

Gadoxetate disodium