Klinefelter SyndromeNCT02526628
Thrombosis and Neurocognition in Klinefelter Syndrome
An observational study of Klinefelter Syndrome and Thrombosis, run by University of Aarhus at 1 site in Denmark.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Klinefelter Syndrome, Thrombosis
- How many people
- 90 participants
- Where
- 1 siteDenmark
- Study dates
- Sep 2015to 21 Aug 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- Klinefelter syndrome with 47 XXY karyotype
- Healthy male
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Haemostatic Balance and Neurocognitive Phenotype in Klinefelter Syndrome - The Effect of Testosterone Treatment
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.
Read the 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
- Keywords
- Testosterone, Neurocognition
- Medical subject headings
- Klinefelter Syndrome, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Time 0 and after 18 months followup
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.
Measured: Time 0 and after 18 months followup
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.
Measured: Time 0 and after 18 months followup
Secondary outcomes (2)
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.
Measured: Time 0 and after 18 months followup
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.
Measured: Once at followup
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2015 (estimated)
- Study startSep 2015
- Primary completion21 Aug 2019
- Study completion21 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Klinefelter SyndromeStudies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Other
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Aarhus University Hospital, Esbjerg Hospital - University Hospital of Southern Denmark, University of Southern Denmark, Sygehus Lillebaelt
- Responsible party
- Sponsor
- Investigators
- Claus H Gravholt, MD, Prof., Study chair, Department of Endocrinology and Internal Medine and Department of Molecular MedicineSimon Chang, MD, Principal investigator, Unit for Thrombosis ResearchAnne Skakkebæk, MD, PhD, Principal investigator, Department of Clinical Genetics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02526628
- Sponsor's protocol ID
- 2015_KS_TESTOSTERONE
- Status last verified
- Jan 2018
- First submitted
- 10 Aug 2015
- Last updated
- 22 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Chang S, Gravholt CH, Skakkebaek A, Munster AB, Palarasah Y. Contact Activation Is Alleviated by Testosterone Replacement Therapy in Klinefelter Syndrome: Evidence of Hormonal and Metabolic Modulation. Andrology. 2026 Mar 27. doi: 10.1111/andr.70220. Online ahead of print.
PubMed 41891299Viuff 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.
PubMed 36978128
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Haemostatic Balance and Neurocognitive Phenotype in Klinefelter Syndrome - The Effect of Testosterone Treatment
- ClinicalTrials.gov ID
- NCT02526628
- Acronym / sponsor ID
- 2015_KS_TESTOSTERONE
- Conditions
- Klinefelter Syndrome, Thrombosis
- Keywords
- Testosterone, Neurocognition
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Aarhus University Hospital, Esbjerg Hospital - University Hospital of Southern Denmark, University of Southern Denmark, Sygehus Lillebaelt
- Study start
- Sep 2015
- Primary completion
- 21 Aug 2019 (actual)
- Study completion
- 21 Aug 2019 (actual)
- First posted
- 18 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- Klinefelter syndrome with 47 XXY karyotype
- Healthy male
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
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.
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.
2 secondary outcomes
Differences in blood coagulation and fibrinolysis parameters between groups
Time frame: Time 0 and after 18 months followup
Differences in fMRI between groups
Time frame: Once at followup
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2019.
- Derived from this study: PubMed 41891299Chang S, Gravholt CH, Skakkebaek A, Munster AB, Palarasah Y. Contact Activation Is Alleviated by Testosterone Replacement Therapy in Klinefelter Syndrome: Evidence of Hormonal and Metabolic Modulation. Andrology. 2026 Mar 27. doi: 10.1111/andr.70220. Online ahead of print.
- Derived from this study: PubMed 36978128Viuff 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claus H Gravholt, MD, Prof. study chair
Department of Endocrinology and Internal Medine and Department of Molecular Medicine
Simon Chang, MD principal investigator
Unit for Thrombosis Research
Anne Skakkebæk, MD, PhD principal investigator
Department of Clinical Genetics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Klinefelter Syndrome and Thrombosis, run by University of Aarhus at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences in thrombin generation (time frame: Time 0 and after 18 months followup). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02526628, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2019.