Trial Title:
Hodgkin's Disease and Chemotherapy Before 40 Years
NCT ID:
NCT06116929
Condition:
Hodgkin Disease
Conditions: Official terms:
Hodgkin Disease
Conditions: Keywords:
Hodgkin Disease
Chemotherapy
Functional and Cognitive Assessment
Study type:
Interventional
Study phase:
N/A
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Prevention
Masking:
None (Open Label)
Intervention:
Intervention type:
Other
Intervention name:
Morphological and functional magnetic resonance imaging (MRI)
Description:
Patients will undergo 3 morphological and functional MRI scans (during rest and activity)
on the 3T MRI scanner at St Philibert Hospital (Lille, France) at 0 (M0), 6 (M6) and 12
(M12) months.
The controls will perform a single functional MRI on the 3T MRI.
Arm group label:
Controls without Hodgkin's disease
Arm group label:
Patients with Hodgkin's disease
Intervention type:
Other
Intervention name:
Neuropsychological assessment
Description:
3 neuropsychological assessments will be carried out at M0, M6 and M12, by the same
neuropsychologist for all patients included.
Controls will undergo the same neuropsychological assessments, but only once.
Arm group label:
Controls without Hodgkin's disease
Arm group label:
Patients with Hodgkin's disease
Summary:
A few studies have focused on other solid cancers (colorectal, prostate). On the other
hand, the study of cognitive impairment in Hodgkin's disease remains less developed, and
structural and functional post-therapy MRI studies have never been carried out. The
impact of cognitive impairment on Hodgkin's disease is rarely, if ever, assessed in
routine clinical practice, despite the fact that it is truly disabling in 16 to 30% of
patients. Cognitive impairment can persist long after diagnosis and treatment. A recent
study examining cognitive functioning in patients an average of 13 years after treatment
found that disorders persisted in 52% of cases, with attentional, working memory and
dysexecutive (planning) difficulties. These disorders have a significant impact on the
daily and professional lives of these young, often working patients. Their rapid
development and persistence after treatment can therefore represent a real limiting
factor, impacting both professional integration and quality of life. Finally, the current
state of knowledge does not allow us to dissociate cognitive disorders from emotional
disorders and fatigue, which represent a major patient complaint. A better definition of
the nature, pathophysiology and specificity of these disorders would therefore enable us
to take better account of their repercussions (social, professional and on quality of
life) and provide better care (in terms of cognitive remediation or psychological
support).
A prospective, longitudinal, multicenter, case-control interventional study in which
cases are patients with Hodgkin's disease (HD) treated with CT +/- radiotherapy and
controls are healthy participants will be conducted. The aim is to study the prevalence
and nature of treatment-induced cognitive impairment and its correlation with emotional
comorbidities, as well as structural and functional brain disorders on MRI. The patient
will thus be his or her own witness, the reference state being that at the time of
diagnosis, before any treatment. The fact that this state has not already been altered by
the disease itself, will be verify thanks to comparison with controls.
Detailed description:
Hodgkin's disease is a neoplasia of lymphoid tissue characterized by the characteristic
presence of Reed Sternberg cells. This disease is preferentially affecting young patients
under the age of 40. It is the leading cause of solid cancer in adolescents and young
adults. At the time of diagnosis, positron emission tomography (PET scan) is used to
determine the stage of the disease. The Ann Arbor classification differentiates between
localized (I-II) and disseminated (III-IV) stages. At St Vincent de Paul Hospital (Lille,
France), 60-70% of diagnoses are performed at a localized stage, versus 30-40% at a
disseminated stage.
Treatment is based on chemotherapy alone (disseminated forms) or a combination of
chemotherapy and radiotherapy (localized forms). The average duration of treatment is
around 5 months for localized forms, and between 6 and 7 months for disseminated forms.
The prognosis is favorable, with a sustained complete remission rate of up to 85% in
patients of all stages. The aim of treatment for these patients is therefore to achieve
complete remission while reducing medium- and long-term side-effects, which could improve
their quality of life.
Recently, treatment strategies have evolved, with de-escalation of chemotherapy
intensity, and strategies guided by early response to Positron emission tomography (PET)
scan have become the norm, in order to significantly reduce the risk of long-term side
effects.
The onset of cognitive and mood disorders in patients undergoing neoplastic treatment,
particularly after chemotherapy, is a frequent and disabling complication. Numerous
studies have identified the occurrence of subjective and objective attentional, memory
and executive disorders. However, these studies are often limited by their small size,
the variability of populations, their heterogeneous design, and the variability of
neuropsychological measures and criteria for defining a cognitive deficit. Furthermore,
the majority of studies have focused on patients treated with chemotherapy (CT) for
breast neoplasia, through neuropsychological assessment and exploration by structural and
functional medical imaging. Thus, the onset of cognitive disorders (more of a
dysexecutive nature) in these patients has been clearly identified, both early at the end
of treatment and over the long term.
Moreover, the social, occupational and quality-of-life repercussions of these disorders
have only recently been explored. However, initial results point to a positive
correlation between subjective perception of cognitive functioning and quality of life.
Nevertheless, the probably multifactorial etiology of these disorders remains unclear. A
recent review of the literature clarifies the factors predisposing to the development of
these cognitive disorders. Factors such as age and genetic polymorphisms in
apolipoprotein E, catechol-O-methyltransferase and Brain-derived neurotrophic factor
(BDNF) may predispose individuals to a higher risk of cognitive disorders. In addition,
changes in brain morphology (reduced grey matter volume) and changes in brain
connectivity could be at the root of these disorders.
In these studies, magnetic resonance imaging (MRI) identified the presence of frontal and
posterior parietal gray matter volume loss in these patients. MRI also provides
information on the structural and functional functioning of brain networks. For example,
changes in the integrity of substance bundles have been identified using the diffusion
tensor technique. In functional MRI (fMRI (BOLD signal)), numerous disturbances have been
identified: hypoactivation of the prefrontal cortex and parietal lobes during activation
of the executive control network, hypoactivation of the prefrontal cortex and hippocampi
during tasks involving working memory, alteration of the dorsal attentional network and
the default mode network.
In addition, one study suggests the presence of pre-treatment network alterations in
patients with breast neoplasia. At pathophysiological level, animal models suggest the
involvement of alterations in neurogenesis, mitochondrial dysfunction or cerebral
cytokine response.
Criteria for eligibility:
Criteria:
Inclusion criteria - case :
- Patient with newly diagnosed Hodgkin's disease
- With intention to treat with chemotherapy +/- radiotherapy
- Aged between 18 and 40 years
- Fluency in French
- Able to undergo neuropsychological evaluation (absence of major sensory disorders)
- Agreeing to take part in the study and having signed the informed consent form
- Affiliated with a social security scheme
Inclusion criteria - controls:
- Individual without Hodgkin's disease
- Aged between 18 and 40
- Proficient in French
- Agreeing to participate in the study and having signed the informed consent form
- Affiliated with a social security scheme
Cases and controls will be matched on age (± 5 years difference), and number of years of
education (difference ≤ 2 years).
Non-inclusion criteria - cases + controls :
- Claustrophobia preventing MRI from being performed
- Contraindication to MRI
- Previous chemotherapy
- History of neurological or psychiatric illness, including severe depression, or
cognitive impairment
- Use of medications that may cause neurological or psychiatric signs
- Alcohol or drug abuse
- Pregnant women
- Persons under guardianship or trusteeship
Gender:
All
Minimum age:
18 Years
Maximum age:
40 Years
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
Centre Hospitalier Artois Ternois
Address:
City:
Arras
Country:
France
Contact:
Last name:
Pauline LIONNE-HUYGHE
Facility:
Name:
Hôpital Claude Huriez
Address:
City:
Lille
Country:
France
Contact:
Last name:
Morgane NUDEL
Facility:
Name:
Hôpital Saint-Philibert
Address:
City:
Lomme
Country:
France
Contact:
Last name:
Bruno LENNE
Facility:
Name:
Hôpital Victor Provo
Address:
City:
Roubaix
Country:
France
Contact:
Last name:
Laurence DETOURMIGNIES
Start date:
May 15, 2024
Completion date:
January 1, 2028
Lead sponsor:
Agency:
Lille Catholic University
Agency class:
Other
Source:
Lille Catholic University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06116929
