Testosterone, Cognition, Ageing, and Cancer

NCT ID: NCT03452436

Last Updated: 2020-03-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 133 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-02-12
• Study Completion Date: 2020-03-01

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.

Conditions

Cancer-related Cognitive Impairment

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Testicular cancer patients

Forty testicular cancer patients included after orchiectomy but prior to any further treatment.

No interventions assigned to this group

Prostate cancer patients

Forty prostate cancer patients included prior to medical castration and radiotherapy.

No interventions assigned to this group

Healthy controls

Forty age- and education-matched healthy controls (20 matched to testicular cancer patients, 20 matched to prostate cancer patients).

No interventions assigned to this group

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Aarhus University Hospital

OTHER

Sponsor Role: collaborator

University of Aarhus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cecilie D R Clausen, MSc

Role: PRINCIPAL_INVESTIGATOR

Unit for Psychooncology & Health Psychology, Department of Oncology, Aarhus University

Robert Zachariae, Professor, DMSc

Role: STUDY_DIRECTOR

Unit for Psychooncology & Health Psychology, Department of Oncology, Aarhus University

Locations

Aarhus University Hospital

Aarhus, , Denmark

Countries

Denmark

Other Identifiers

TCAC

Identifier Type: -

Identifier Source: org_study_id