Thrombosis and Neurocognition in Klinefelter Syndrome

NCT ID: NCT02526628

Last Updated: 2019-08-22

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 90 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2019-08-21

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.

Conditions

Klinefelter Syndrome; Thrombosis

Study Design

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

Study Groups

Testosterone naïve KS

Men with Klinefelter syndrome without testosterone treatment. After initial examination standard treatment with testosterone will be effectuated according to current guidelines.

No interventions assigned to this group

Testosterone treated KS

Men with Klinefelter syndrome receiving testosterone treatment

No interventions assigned to this group

Controls 1

Matched healthy male controls for testosterone naive KS

No interventions assigned to this group

Controls 2

Matched healthy male controls for testosterone treated KS

No interventions assigned to this group

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Aarhus University Hospital

OTHER

Sponsor Role: collaborator

Esbjerg Hospital - University Hospital of Southern Denmark

OTHER

Sponsor Role: collaborator

University of Southern Denmark

OTHER

Sponsor Role: collaborator

Sygehus Lillebaelt

OTHER

Sponsor Role: collaborator

University of Aarhus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Claus H Gravholt, MD, Prof.

Role: STUDY_CHAIR

Department of Endocrinology and Internal Medine and Department of Molecular Medicine

Simon Chang, MD

Role: PRINCIPAL_INVESTIGATOR

Unit for Thrombosis Research

Anne Skakkebæk, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Clinical Genetics

Locations

Department for Endocrinology and Internal Medicine

Aarhus, , Denmark

Countries

Denmark

References

Viuff M, Skakkebaek A, Johannsen EB, Chang S, Pedersen SB, Lauritsen KM, Pedersen MGB, Trolle C, Just J, Gravholt CH. X chromosome dosage and the genetic impact across human tissues. Genome Med. 2023 Mar 28;15(1):21. doi: 10.1186/s13073-023-01169-4.

Reference Type: DERIVED

PMID: 36978128 (View on PubMed)

Other Identifiers

2015_KS_TESTOSTERONE

Identifier Type: -

Identifier Source: org_study_id