Clinical trial NCT02526628: Thrombosis and Neurocognition in Klinefelter Syndrome
Official title: The Haemostatic Balance and Neurocognitive Phenotype in Klinefelter Syndrome - The Effect of Testosterone Treatment
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Klinefelter Syndrome
Thrombosis
Keywords: Testosterone
Neurocognition
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
name: Esbjerg Hospital - University Hospital of Southern Denmark
name: University of Southern Denmark
name: Sygehus Lillebaelt
First posted: 2015-08-18
Enrollment: 90
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Men with Klinefelter syndrome identified through clinics for fertility, endocrinology and genetics. Healthy controls from the general population living in Central Denmark Region.

Brief summary: The haemostatic balance and neurocognitive capability of men with Klinefelter syndrome is compared to healthy controls by using specific biochemical assays for coagulation and fibrinolysis and a selection of neuropsychological tests and brain fMRI. Furthermore, the effect of gonadal status and any effects of long- or short-term testosterone treatment on the above mentioned parameters are investigated.

Detailed description: Klinefelter syndrome (KS) affects approximately 1 in every 600 males, but remains severely underdiagnosed. Men with KS are more prone to a wide range of diseases including thrombotic disorders. Also, neurocognitive function is impaired in KS. The background for the increased thrombosis proneness is not understood, and also it is not understood how testosterone treatment affects the thrombosis risk in KS. The effects of testosterone treatment on neurocognition in KS is also not completely understood. However, it is speculated that testosterone treatment at an early point could help improve the overall neurocognitive performance.

In this study 30 males with KS receiving testosterone treatment, 30 males with KS not receiving testosterone treatment and 60 matched healthy male controls are included. After initial examination including blood testing and neurocognitive testing, the subjects are followed for 18 months and examined a second time. After initial examination the group of previously untreated KS males will be put on standard testosterone treatment according to current guidelines.

Groups will be compared by measuring and array of markers for coagulation and fibrinolysis, including thrombin generation and fibrin structure analysis, to assess the haemostatic balance. Also, a wide array of neurocognitive tests and brain fMRI is applied to compare the neurocognitive function between the groups.

Eligibility criteria: Inclusion Criteria:

* Klinefelter syndrome with 47 XXY karyotype
* Healthy male

Exclusion Criteria:

* Known thrombophilia
* Previous thrombotic event
* Chronic or acute illness affecting the haemostatic balance (e.g. diabetes, cancer).
* Previous or current disease affecting the brain
* Weight above 120 kg
* Current abuse of stimulants affecting the brain
* Unability to complete MR-scan (e.g. claustrophobia, internal metal objects)

Primary outcomes:
measure: Differences in thrombin generation
timeFrame: Time 0 and after 18 months followup
measure: Differences in fibrin clot properties
timeFrame: Time 0 and after 18 months followup
measure: Difference in neurocognition
timeFrame: Time 0 and after 18 months followup
Secondary outcomes:
measure: Differences in blood coagulation and fibrinolysis parameters between groups
timeFrame: Time 0 and after 18 months followup
measure: Differences in fMRI between groups
timeFrame: Once at followup
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Department for Endocrinology and Internal Medicine
Study officials:
affiliation: Department of Endocrinology and Internal Medine and Department of Molecular Medicine
name: Claus H Gravholt, MD, Prof.
role: STUDY_CHAIR
affiliation: Unit for Thrombosis Research
name: Simon Chang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Clinical Genetics
name: Anne Skakkebæk, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: