Clinical trial NCT04630275: Gonadal Dysfunction in Male Long-term Survivors of Malignant Lymphoma; Vitality-Obs
Official title: Vitality-Obs; An Observational and Descriptive Cross-sectional Study of Gonadal Dysfunction in Male Long-term Survivors of Malignant Lymphoma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hypogonadism
Keywords: lymphoma
Diffuse Large B-Cell Lymphoma
Hodgkin
hypogonadism
testosterone
EORTC
Quality of life
Sexuality
Sexual health
Cancer
IIEF-5
Doxorubicin
anthracycline
Leydig cells
Hypothalamus
adriamycin
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
First posted: 2020-11-16
Enrollment: 172
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A cohort of patients with Hodgkin Lyphoma or Diffuse Large B-Cell Lymphoma diagnosed during the period April 2008- April 2018 at the Departments of Hematology, Herlev Hospital, Copenhagen University Hospital and Zealand University Hospital, will be identified through The Danish Lymphoma registry (LyFo).

Brief summary: This study is an observational cross-sectional study which aims to investigate the relationship between treatment with chemotherapy and the development of low levels of testosterone in the blood in patients cured for aggressive lymphoma. We hypothesize that patients in turn will develop sexual dysfunction and poor quality of life because of this reduced level of testosterone. Cancer treatment is increasingly effective and the overall survival higher, which makes issues like sexuality and long-term quality of life more and more important to address in cured cancer patients. Patient sexuality and quality of life is measured by 3 questionnaires filled out once, and serum testosterone by a single blood sample. If serum testosterone is in the lower part of the normal reference interval, patients will be offered further hormonal evaluation by department of growth and reproduction at Copenhagen University Hospital. We hope to show that future follow up visits should include focus on sexuality and serum testosterone. Questionnaires and blood samples can be implemented easily and without great cost.

Detailed description: Diffuse large B-cell lymphoma and Hodgkin Lymphoma are two aggressive lymphomas often treated with doxorubicin containing chemotherapy. Doxorubicin is an anthracycline and is known to be toxic to both Leydig Cells of the testes and hormone-producing cells of the hypothalamus. Therefore patients treated with this drug are at risk of developing hypogonadism. Standard follow-up programs do not include investigation of hormone levels. With this study we aim to investigate the extent of hypogonadisme in patients treated with anthracycline containing chemotherapy, to clarify whether it is relevant to include serum testosterone in standard follow-up programs.

Our Hypothesis:

Hypothesis 1: A significant proportion of long-term male survivors of HL and DLBCL have impaired QoL due to sexual dysfunction.

Hypothesis 2: A significant proportion of long-term male survivors of HL and DLBCL have reduced levels of testosterone.

Hypothesis 3: A significant relationship between QoL, sexual dysfunction and testosterone levels exists.

To clarify the extent of hypogonadisme a single blood test including s-total-testosterone will be drawn once, and levels below age adjusted reference levels will be classified as hypogonadisme. To assess patients sexuality and quality of life, 3 questionnaires will be filled out; the EORTC QLQ-C30 for general quality of life, EORTC SHQ-22 for sexual health and IIEF-5 for sexual function.

To evaluate whether normal reference levels are sufficient in the examination of lymphoma survivors, included men with serum testosterone in the lower part of the normal reference interval will be offered further hormonal evaluation at the department of growth and reproduction at Copenhagen University hospital. Blood test results will be evaluted by this research group.

Eligibility criteria: Inclusion Criteria:

1. Age 18-65 years at follow-up
2. Male
3. Verified diagnosis of de novo DLBCL or classical HL diagnosed between April 2008 and April 2018 according to WHO classification.
4. Completed curative intent first line treatment with anthracycline-containing chemotherapy with or without consolidating radiotherapy, with disease in complete remission at EOT-PET/CT at least one year prior to inclusion.
5. Literate in Danish

Exclusion Criteria:

1. Concurrent low-grade lymphoma
2. Current or prior lymphoproliferative disease of the central nervous system (CNS)
3. Current or prior lymphoproliferative disease of the testes
4. Mental or physical conditions that are expected to prevent the necessary "compliance" and/or "adherence" in relation to the study procedures.
5. Treatment with second line chemotherapy or high dose therapy.
6. Current or prior anabolic steroid drug abuse

Primary outcomes:
measure: Serum-testosterone level
timeFrame: At inclusion
Secondary outcomes:
measure: Frequency of co-morbidity according to Cumulative Illness Rating Scale (CIRS) score
timeFrame: At inclusion
measure: Frequency of Erectile Function according to International Index of Erectile Function (IIEF-5)
timeFrame: At inclusion
measure: Level of sexual dysfunction symptoms
timeFrame: At inclusion
measure: Level of sexual function
timeFrame: At inclusion
measure: Level of Quality of life, functioning
timeFrame: At inclusion
measure: Level of Quality of life, symptoms
timeFrame: At inclusion
measure: Level of Quality of life, global health
timeFrame: At inclusion
measure: serum sex hormone binding globulin (SHBG)
timeFrame: Through study completion, up to two years after incusion.
measure: Serum Luteinizing hormone (LH)
timeFrame: Through study completion, up to two years after incusion.
measure: Serum Inhibin B
timeFrame: Through study completion, up to two years after incusion.
measure: Serum Follicle stimulating hormone (FSH)
timeFrame: through study completion, up to two years after inclusion
measure: Serum Estradiol
timeFrame: through study completion, up to two years after inclusion
measure: Serum INSL-3
timeFrame: through study completion, up to two years after inclusion
measure: Serum hemoglobin
timeFrame: through study completion, up to two years after inclusion
measure: Serum hematocrit
timeFrame: through study completion, up to two years after inclusion
measure: Serum free testosterone
timeFrame: through study completion, up to two years after inclusion
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital
city: Herlev
country: Denmark
facility: Herlev University Hospital
city: Roskilde
country: Denmark
facility: Zealand University Hospital
Study officials:
References: