Thrombosis and Neurocognition in Klinefelter Syndrome

Thrombosis Clinical Trial

Official title:

The Haemostatic Balance and Neurocognitive Phenotype in Klinefelter Syndrome - The Effect of Testosterone Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02526628
• Other study ID #: 2015_KS_TESTOSTERONE
• Status: Completed
• Start date: September 2015
• Est. completion date: August 21, 2019

Study information

• Verified date: January 2018
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: August 21, 2019
• Est. primary completion date: August 21, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Klinefelter Syndrome
• Syndrome
• Thrombosis

Locations

Country	Name	City	State
Denmark	Department for Endocrinology and Internal Medicine	Aarhus

Sponsors (5)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital, Hospital of South West Denmark, Sygehus Lillebaelt, University of Southern Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences in thrombin generation	Thrombin generation using the CAT assay is assessed as ETP (nM thrombin), peak height (nM thrombin) and lag time (minutes). All variables are assessed at inclusion and after a 18 month follow-up. Groups are compared statistically at each time point and any changes during follow-up is also analysed.	Time 0 and after 18 months followup
Primary	Differences in fibrin clot properties	Fibrin clot properties is assessed by fibrin structure analysis in plasma samples. All variables are assessed at inclusion and after a 18 month follow-up. Groups are compared statistically at each time point and any changes during follow-up is also analysed.	Time 0 and after 18 months followup
Primary	Difference in neurocognition	neurocognition is assessed using a wide array of psychological tests (e.g. Wais-III, Stroop test, Wisconsin Card Sorting Test and others) All variables are assessed at inclusion and after a 18 month follow-up. Groups are compared statistically at each time point and any changes during follow-up is also analysed.	Time 0 and after 18 months followup
Secondary	Differences in blood coagulation and fibrinolysis parameters between groups	Coagulation and fibrinolysis can not be adequately assessed by analysis of a single parameter. To evaluate the overall status of these systems an array of analyses are needed, and further more need to be interpreted by experts within the field. Thus, severeal markers of coagulation and fibrinolysis including INR, APTT, single coagulation factors, PAI-1 and others are to be assessed at inclusion and after a 18 month follow-up. Groups are compared statistically at each time point and any changes during follow-up is also analysed. Besides applying statistics, the compiled results will also be interpreted by experts within the field to provide an overall characterization of the haemostatic balance in the individual groups and by comparison to each other.	Time 0 and after 18 months followup
Secondary	Differences in fMRI between groups	fMRI will be performed to evaluate the response in the brain to various stimuli and tests, with the overall purpose of examining speech, memory and other cognition related features.	Once at followup