Clinical trial NCT03452436: Testosterone, Cognition, Ageing, and Cancer
Official title: Testosterone, Cognition, Ageing, and Cancer - A Controlled, Prospective Study About the Association Between Testosterone and the Prevalence and Severity of Cancer Related Cognitive Impairment in Testicular and Prostate Cancer Patients.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cancer-related Cognitive Impairment
Keywords: Cancer-related Cognitive Impairment
Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorder
Testosterone
Endocrinology
Testicular Cancer
Prostate Cancer
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
First posted: 2018-03-02
Enrollment: 133
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Men with testicular and prostate cancer seen at Aarhus University Hospital. Age- and education matched healthy controls recruited from the general population of Central Denmark Region.

Brief summary: The primary aim of the study is - in a prospective controlled design - to examine whether treatment-induced decreases in testosterone acts as a mechanism of cancer-related cognitive impairment (CRCI) in testicular and prostate cancer patients.

Secondary aims are 1) to explore whether decreases in testosterone interacts with increasing age to cause more severe CRCI in older patients, 2) to explore underlying neurophysiological (brain morphology) mechanisms of CRCI, and 3) to evaluate selected genetic variants as possible moderators of CRCI.

Detailed description: The study will include three groups with a total of 120 participants: A) Forty testicular cancer patients will be included and examined 1) shortly after orchiectomy and prior to any further treatment and 2) at 6 months' follow- up. B) Forty prostate cancer patients will be included and examined at two time-points: 1) prior to initiation of medical castration and radiotherapy and 2) at 6 months' follow- up. C) Forty age- and education-matched healthy controls will be included and assessed at a similar time-interval, i.e., at an initial examination and at a 6 month follow-up. Measures include a battery of neuropsychological/ cognitive tests, questionnaires, blood samples, and Magnetic Resonance Imaging (MRI).

Primary hypothesis

1. Treatment-induced decreases in testosterone will be associated with decline in global cognitive functioning from baseline to 6 months' follow- up in both testicular and prostate cancer patients.

   Secondary hypotheses
2. Treatment-induced decreases in testosterone will be associated with decline in individual cognitive domains (i.e., processing speed, attention, verbal fluency, executive functioning, working memory, verbal learning and memory, visuospatial learning and memory, and visuospatial ability) from baseline to 6 months' follow- up in both testicular and prostate cancer patients.
3. Decline in cognitive functioning from baseline to 6 months' follow- up in both testicular and prostate cancer patients will correspond to changes in grey matter as measured by T1-weighted MRI.
4. Decline in cognitive functioning from baseline to 6 months' follow- up in both testicular and prostate cancer patients will correspond to changes in brain white matter as measured with diffusion-weighted MRI.
5. Treatment-induced decreases in testosterone will be more strongly associated with decline in cognitive functioning in prostate cancer patients compared with testicular cancer patients due to more advanced age in the former group.
6. Treatment-induced decreases in testosterone will be more strongly associated with decline in cognitive functioning in both testicular and prostate cancer patients carrying the the Apolipoprotein E (APOE) ε4 allele, the Val catechol-O-methyltranferase (COMT) allele, the Val/Val Brain- derived neurotrophic factor (BDNF) genotype, and a short polymorphic CAG repeat length of the Androgen Receptor (AR) gene.
7. Treatment-induced decreases in testosterone will be associated with increases in neurobehavioral symptoms (i.e., apathy, executive dysfunction, and disinhibition) from baseline to 6 months' follow- up in both testicular and prostate cancer patients.
8. Treatment-induced decreases in testosterone will be associated with decreases in health-related quality of life from baseline to 6 months' follow- up in both testicular and prostate cancer patients.
9. Treatment-induced decreases in testosterone will be associated with decreases in perceived cognitive functioning from baseline to 6 months' follow- up in both testicular and prostate cancer patients.

Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of testicular cancer
* Confirmed diagnosis of prostate cancer and prescription of medical castration and radiotherapy

Exclusion Criteria:

* Previous cancer disease
* Previous central nervous system disease
* Brain metastases
* Severe psychiatric disease (e.g., schizophrenia, major depressive disorder)
* Insufficient Danish proficiency for neuropsychological testing

Primary outcomes:
measure: Global cognitive functioning
timeFrame: Baseline and 6 months' follow-up
Secondary outcomes:
measure: Visuospatial ability
timeFrame: Baseline and 6 months' follow-up
measure: Visuospatial ability
timeFrame: Baseline and 6 months' follow-up
measure: Visuospatial ability
timeFrame: Baseline and 6 months' follow-up
measure: Visuospatial ability
timeFrame: Baseline and 6 months' follow-up
measure: Processing speed
timeFrame: Baseline and 6 months' follow-up
measure: Processing speed
timeFrame: Baseline and 6 months' follow-up
measure: Attention
timeFrame: Baseline and 6 months' follow-up
measure: Executive functioning
timeFrame: Baseline and 6 months' follow-up
measure: Executive functioning
timeFrame: Baseline and 6 months' follow-up
measure: Working memory
timeFrame: Baseline and 6 months' follow-up
measure: Working memory
timeFrame: Baseline and 6 months' follow-up
measure: Verbal fluency
timeFrame: Baseline and 6 months' follow-up
measure: Verbal learning and memory
timeFrame: Baseline and 6 months' follow-up
measure: Visuospatial learning and memory
timeFrame: Baseline and 6 months' follow-up
measure: Testosterone levels
timeFrame: Baseline and 6 months' follow-up
measure: Brain grey matter
timeFrame: Baseline and 6 months' follow-up
measure: Brain white matter
timeFrame: Baseline and 6 months' follow-up
measure: Moderator: APOE genotype
timeFrame: Baseline
measure: Moderator: COMT genotype
timeFrame: Baseline
measure: Moderator: BDNF genotype
timeFrame: Baseline
measure: Moderator: CAG repeat length of the AR gene
timeFrame: Baseline
measure: Neurobehavioral symptoms (i.e., apathy, executive dysfunction, and disinhibition)
timeFrame: Baseline and 6 months' follow-up
measure: Perceived cognitive functioning
timeFrame: Baseline and 6 months' follow-up
measure: Health-related quality of life
timeFrame: Baseline and 6 months' follow-up
measure: Health-related quality of life - Prostate Cancer
timeFrame: Baseline and 6 months' follow-up
measure: Health-related quality of life - Testicular Cancer
timeFrame: Baseline and 6 months' follow-up
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
Study officials:
affiliation: Unit for Psychooncology & Health Psychology, Department of Oncology, Aarhus University
name: Cecilie D R Clausen, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Unit for Psychooncology & Health Psychology, Department of Oncology, Aarhus University
name: Robert Zachariae, Professor, DMSc
role: STUDY_DIRECTOR
References: