Brain Integrity in Survivors of Hodgkin Lymphoma Treated With Thoracic Radiation

NCT ID: NCT01820117

Last Updated: 2018-03-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

416 participants

Study Classification

OBSERVATIONAL

Study Start Date

2013-04-26

Study Completion Date

2018-02-20

Brief Summary

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While thoracic radiation therapy (TRT) has been a primary component in successful treatment of a variety of childhood and adult cancers, the exposure to this treatment has been associated with significant cardiovascular and pulmonary morbidity in long-term survivors. Within non-cancer populations, cardiovascular and pulmonary morbidity is associated with increased risk for cerebral vascular accidents (CVAs), accelerated brain atrophy and neurocognitive impairment. Patients with chronic heart disease demonstrate problems with attention, processing speed, memory, and executive functions. Chronic pulmonary disease also increases the risk of stroke, leukoencephalopathy, and neurocognitive impairment in non-cancer populations. The investigators propose to examine indices of brain integrity, including neurocognitive performance and brain MRI/MRA, in long-term adult survivors of Hodgkin lymphoma (HL) treated with thoracic radiation and no direct central nervous system therapy.

OBJECTIVES:

1. To evaluate brain integrity in adult survivors of childhood HL treated with thoracic radiation therapy.
2. To identify therapeutic factors associated with brain integrity in adult survivors of childhood HL who are at risk for cardiac and pulmonary morbidity.
3. To examine associations between cardiac, vascular and pulmonary health and brain integrity in adult survivors of childhood HL treated with thoracic radiation.

Detailed Description

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This is an observational study to collect health data from long-term survivors of Hodgkin lymphoma (HL). Data will be collected once at participant enrollment. The long-term effects of thoracic radiation therapy (TRT) given earlier as part of the treatment for HL will be examined in long-term survivors and compared to health data collected from normal volunteers.

HL survivors who were treated at St. Jude Children's Research Hospital (SJCRH) with TRT will be recruited to complete a comprehensive neurocognitive evaluation, brain MRI/MRA, a clinical neurological exam, peripheral pulse contour analysis, non-invasive central blood pressure monitoring, cardiopulmonary exercise testing, and serum biomarkers related to cardiac disease. As part of their standard St. Jude LIFE protocol evaluation, they also complete an echocardiogram, pulmonary function tests and questionnaires designed to evaluate broad health, psychological, socioeconomic and environmental factors that impact everyday life.

A comparison sample of healthy individuals, frequency-matched on age, sex and race will also be recruited. The comparison group will complete the comprehensive neurocognitive evaluation, brain MRI/MRA, clinical neurological exam, pulse contour analysis, non-invasive central blood pressure monitoring, and cardiopulmonary exercise testing. Through the St. Jude LIFE protocol, the comparison sample will also complete an echocardiogram, pulmonary function tests and questionnaires designed to evaluate broad health, psychological, socioeconomic and environmental factors that impact everyday life.

Conditions

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Hodgkin Lymphoma

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

OTHER

Study Groups

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Hodgkin lymphoma

Participants previously treated at St. Jude Children's Research Hospital with thoracic radiation therapy for Hodgkin lymphoma.

Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.

Neurocognitive Evaluation

Intervention Type OTHER

The neurocognitive evaluation will include measures of academic achievement, intelligence, sustained attention, memory, processing speed, executive functions, functional behavior, and emotional functioning.

Quantitative Brain Imaging

Intervention Type OTHER

Imaging will include raw images to both quantify white matter hyperintensities and hemosiderin deposits, as well as cortical thickness and tissue segmentation. Brain imaging will be repeated on participants who are concurrently enrolled on BRIGHT and MIND protocols at St. Jude and who completed prior brain imaging during the BRIGHT clinic visit. The repeat MRI will be done at their 6 month MIND clinic visit.

Neurologic Evaluation

Intervention Type OTHER

Evaluation includes a complete review of neurologic symptoms, and interview and examination by the neurologist, assessment of neurologic symptoms and determination of their impact on day-to-day living, and quantified neurologic examination by the neurologist.

Health Questionnaire

Intervention Type OTHER

Participants will be asked to complete an approximately 450-item survey to assess health history and status, social and demographic factors, health behaviors, and psychosocial constructs.

Vascular Testing

Intervention Type OTHER

Digital assessment of endothelial function will be studied, and central blood and pulse pressure and carotid-femoral pulse wave velocity will be non-invasively measured.

Cardiopulmonary Exercise Testing

Intervention Type OTHER

Study participants will undergo cardiopulmonary exercise testing by treadmill. Those participants whose physical performance does not permit walking safely on the treadmill (extreme deconditioning, lower extremity paralysis, balance disorder, acute lower extremity injury) will perform cardiopulmonary exercise testing on a bicycle or upper extremity ergometer using a comparable testing protocol.

Echocardiography

Intervention Type OTHER

A complete 3D as well as 2D echocardiogram with Doppler and M-mode will be performed.

Pulmonary Function Testing

Intervention Type OTHER

Pulmonary function testing will include spirometry, lung volume measurements by body plethysmography, and single-breath carbon monoxide-diffusion capacity (DLCO).

Serum Biomarkers

Intervention Type PROCEDURE

Blood for serum biomarkers associated with cardiovascular morbidity will be drawn, including high-sensitivity C-reactive protein, serum homocysteine.

Ophthalmology Examination

Intervention Type OTHER

Ophthalmology examination will include a review of symptoms, examination, and fundus imaging. The examination will consist of visual acuity testing, refraction testing, retinoscopy, ocular pressure, and examination under mydriasis. Fundus photography will be used to capture an image of the retina for examination of potential hypertensive retinopathy.

Normal control

A group of healthy individuals matched for age, sex and race.

Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.

Neurocognitive Evaluation

Intervention Type OTHER

The neurocognitive evaluation will include measures of academic achievement, intelligence, sustained attention, memory, processing speed, executive functions, functional behavior, and emotional functioning.

Quantitative Brain Imaging

Intervention Type OTHER

Imaging will include raw images to both quantify white matter hyperintensities and hemosiderin deposits, as well as cortical thickness and tissue segmentation. Brain imaging will be repeated on participants who are concurrently enrolled on BRIGHT and MIND protocols at St. Jude and who completed prior brain imaging during the BRIGHT clinic visit. The repeat MRI will be done at their 6 month MIND clinic visit.

Neurologic Evaluation

Intervention Type OTHER

Evaluation includes a complete review of neurologic symptoms, and interview and examination by the neurologist, assessment of neurologic symptoms and determination of their impact on day-to-day living, and quantified neurologic examination by the neurologist.

Health Questionnaire

Intervention Type OTHER

Participants will be asked to complete an approximately 450-item survey to assess health history and status, social and demographic factors, health behaviors, and psychosocial constructs.

Vascular Testing

Intervention Type OTHER

Digital assessment of endothelial function will be studied, and central blood and pulse pressure and carotid-femoral pulse wave velocity will be non-invasively measured.

Cardiopulmonary Exercise Testing

Intervention Type OTHER

Study participants will undergo cardiopulmonary exercise testing by treadmill. Those participants whose physical performance does not permit walking safely on the treadmill (extreme deconditioning, lower extremity paralysis, balance disorder, acute lower extremity injury) will perform cardiopulmonary exercise testing on a bicycle or upper extremity ergometer using a comparable testing protocol.

Echocardiography

Intervention Type OTHER

A complete 3D as well as 2D echocardiogram with Doppler and M-mode will be performed.

Pulmonary Function Testing

Intervention Type OTHER

Pulmonary function testing will include spirometry, lung volume measurements by body plethysmography, and single-breath carbon monoxide-diffusion capacity (DLCO).

Serum Biomarkers

Intervention Type PROCEDURE

Blood for serum biomarkers associated with cardiovascular morbidity will be drawn, including high-sensitivity C-reactive protein, serum homocysteine.

Ophthalmology Examination

Intervention Type OTHER

Ophthalmology examination will include a review of symptoms, examination, and fundus imaging. The examination will consist of visual acuity testing, refraction testing, retinoscopy, ocular pressure, and examination under mydriasis. Fundus photography will be used to capture an image of the retina for examination of potential hypertensive retinopathy.

Interventions

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Neurocognitive Evaluation

The neurocognitive evaluation will include measures of academic achievement, intelligence, sustained attention, memory, processing speed, executive functions, functional behavior, and emotional functioning.

Intervention Type OTHER

Quantitative Brain Imaging

Imaging will include raw images to both quantify white matter hyperintensities and hemosiderin deposits, as well as cortical thickness and tissue segmentation. Brain imaging will be repeated on participants who are concurrently enrolled on BRIGHT and MIND protocols at St. Jude and who completed prior brain imaging during the BRIGHT clinic visit. The repeat MRI will be done at their 6 month MIND clinic visit.

Intervention Type OTHER

Neurologic Evaluation

Evaluation includes a complete review of neurologic symptoms, and interview and examination by the neurologist, assessment of neurologic symptoms and determination of their impact on day-to-day living, and quantified neurologic examination by the neurologist.

Intervention Type OTHER

Health Questionnaire

Participants will be asked to complete an approximately 450-item survey to assess health history and status, social and demographic factors, health behaviors, and psychosocial constructs.

Intervention Type OTHER

Vascular Testing

Digital assessment of endothelial function will be studied, and central blood and pulse pressure and carotid-femoral pulse wave velocity will be non-invasively measured.

Intervention Type OTHER

Cardiopulmonary Exercise Testing

Study participants will undergo cardiopulmonary exercise testing by treadmill. Those participants whose physical performance does not permit walking safely on the treadmill (extreme deconditioning, lower extremity paralysis, balance disorder, acute lower extremity injury) will perform cardiopulmonary exercise testing on a bicycle or upper extremity ergometer using a comparable testing protocol.

Intervention Type OTHER

Echocardiography

A complete 3D as well as 2D echocardiogram with Doppler and M-mode will be performed.

Intervention Type OTHER

Pulmonary Function Testing

Pulmonary function testing will include spirometry, lung volume measurements by body plethysmography, and single-breath carbon monoxide-diffusion capacity (DLCO).

Intervention Type OTHER

Serum Biomarkers

Blood for serum biomarkers associated with cardiovascular morbidity will be drawn, including high-sensitivity C-reactive protein, serum homocysteine.

Intervention Type PROCEDURE

Ophthalmology Examination

Ophthalmology examination will include a review of symptoms, examination, and fundus imaging. The examination will consist of visual acuity testing, refraction testing, retinoscopy, ocular pressure, and examination under mydriasis. Fundus photography will be used to capture an image of the retina for examination of potential hypertensive retinopathy.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Current St. Jude LIFE protocol Participant, treated with thoracic radiation
* Currently ≥ 18 years of age
* ≥ 10 years from original diagnosis


* Research participant is a sibling, parent, relative or friend of a current or former St. Jude patient
* Research participant must be at least 18 years of age at the time of the scheduled evaluation

Exclusion Criteria

* Has participated in the previous pilot study at St. Jude (HPP16)
* History of cranial or total-body radiation therapy
* History of intrathecal Methotrexate, high-dose Methotrexate or high-dose Cytarabine.
* History of head injury or diagnosis of a genetic disorder associated with neurocognitive impairment
* Pre-existing known neurocognitive impairment prior to diagnosis of Hodgkin lymphoma
* History of congenital heart disease reported in the literature to be associated with neurocognitive status as determined by the principal investigators
* Currently pregnant
* Secondary central nervous system neoplasm


* History of cranial, total-body or thoracic radiation therapy
* History of intrathecal Methotrexate, high-dose Methotrexate, or high-dose Cytarabine.
* History of head injury or diagnosis of a genetic disorder associated with neurocognitive impairment
* Known neurocognitive impairment
* History of congenital heart disease reported in the literature to be associated with neurocognitive status as determined by the principal investigators
* Currently pregnant
* Central nervous system neoplasm
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kevin Krull, PhD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

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St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Countries

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United States

Related Links

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http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

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R01CA174794

Identifier Type: NIH

Identifier Source: secondary_id

View Link

BRIGHT

Identifier Type: -

Identifier Source: org_study_id

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