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Thrombosis and Neurocognition in Klinefelter Syndrome

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ClinicalTrials.gov Identifier: NCT02526628
Recruitment Status : Completed
First Posted : August 18, 2015
Last Update Posted : August 22, 2019
Sponsor:
Collaborators:
Aarhus University Hospital
Hospital of South West Denmark
University of Southern Denmark
Sygehus Lillebaelt
Information provided by (Responsible Party):
University of Aarhus

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.

Condition or disease
Klinefelter Syndrome Thrombosis

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.


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Study Type : Observational
Actual Enrollment : 90 participants
Observational Model: Case-Control
Time Perspective: Other
Official Title: The Haemostatic Balance and Neurocognitive Phenotype in Klinefelter Syndrome - The Effect of Testosterone Treatment
Study Start Date : September 2015
Actual Primary Completion Date : August 21, 2019
Actual Study Completion Date : August 21, 2019

Resource links provided by the National Library of Medicine


Group/Cohort
Testosterone naïve KS
Men with Klinefelter syndrome without testosterone treatment. After initial examination standard treatment with testosterone will be effectuated according to current guidelines.
Testosterone treated KS
Men with Klinefelter syndrome receiving testosterone treatment
Controls 1
Matched healthy male controls for testosterone naive KS
Controls 2
Matched healthy male controls for testosterone treated KS



Primary Outcome Measures :
  1. Differences in thrombin generation [ Time Frame: Time 0 and after 18 months followup ]
    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.

  2. Differences in fibrin clot properties [ Time Frame: Time 0 and after 18 months followup ]
    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.

  3. Difference in neurocognition [ Time Frame: Time 0 and after 18 months followup ]
    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.


Secondary Outcome Measures :
  1. Differences in blood coagulation and fibrinolysis parameters between groups [ Time Frame: Time 0 and after 18 months followup ]
    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.

  2. Differences in fMRI between groups [ Time Frame: Once at followup ]
    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.


Biospecimen Retention:   Samples With DNA
Bloodsamples


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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.
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)

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02526628


Locations
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Denmark
Department for Endocrinology and Internal Medicine
Aarhus, Denmark, 8000
Sponsors and Collaborators
University of Aarhus
Aarhus University Hospital
Hospital of South West Denmark
University of Southern Denmark
Sygehus Lillebaelt
Investigators
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Study Chair: Claus H Gravholt, MD, Prof. Department of Endocrinology and Internal Medine and Department of Molecular Medicine
Principal Investigator: Simon Chang, MD Unit for Thrombosis Research
Principal Investigator: Anne Skakkebæk, MD, PhD Department of Clinical Genetics

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Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT02526628     History of Changes
Other Study ID Numbers: 2015_KS_TESTOSTERONE
First Posted: August 18, 2015    Key Record Dates
Last Update Posted: August 22, 2019
Last Verified: January 2018
Keywords provided by University of Aarhus:
Testosterone
Neurocognition
Additional relevant MeSH terms:
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Klinefelter Syndrome
Thrombosis
Syndrome
Disease
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Sex Chromosome Disorders of Sex Development
Disorders of Sex Development
Urogenital Abnormalities
Sex Chromosome Disorders
Chromosome Disorders
Congenital Abnormalities
Genetic Diseases, Inborn
Gonadal Disorders
Endocrine System Diseases
Hypogonadism
Methyltestosterone
Testosterone
Testosterone undecanoate
Testosterone enanthate
Testosterone 17 beta-cypionate
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents