Clinical trial NCT00999310: Neuropsychologic, Neuroradiologic, Endocrinologic, and Genetic Aspects of Klinefelter Syndrome
Official title: Neuropsychologic, Neuroradiologic, Endocrinologic, and Genetic Aspects of Klinefelter Syndrome
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Klinefelter Syndrome
Keywords: Klinefelter syndrome
Neuropsychology
Neuroradiology
Genetics
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
First posted: 2009-10-21
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with Klinefelter syndrome are recruited from endocrine and fertility clinics.

The control groups are recruited by advertising for healthy volunteers at the University of Aarhus and at the Blood Bank at the Aarhus University Hospital.

Brief summary: The purpose of this study is to investigate the following:

1. Whether Klinefelter Syndrome is associated with altered total and regional brain volumes and altered brain activity.
2. The influence of genetic factors and testosterone treatment on the neuropsychological phenotype, total and regional brain volumes and brain activity in men with Klinefelter syndrome.

Detailed description: Klinefelter syndrome (KS) is the most common sex-chromosome disorder in men with a prevalence of 1 in 660 men. Men with the syndrome have an additional X-chromosome. The syndrome is associated with cognitive and behavioral dysfunction and also with hypogonadism. Magnetic resonance imaging have pointed to different volumetric alterations in several brain structures. Several genetic factors involving the X-chromosome have been suggested to influence the neuropsychological phenotype in men with KS.

The aim of this study is to investigate the following: 1.Whether KS is associated with altered total and regional brain volumes and altered brain activity. 2.Whether genetic factors influence the neuropsychological phenotype, total and regional brain volumes, and brain activity in men with KS. 3.Whether testosterone treatment improves cognitive skills and change brain activity in men with KS.

Participants are divided in 5 groups: 1. 50 men with KS who receive testosterone treatment. 2. 50 men KS who do not receive testosterone treatment. 3. 100 age-matched control men.4. 50 age-matched control women are included as a control group for X-chromosome inactivation pattern. 5. Parents of KS subjects in group 1 and 2 are included to determine the parental origin of the supernumerary X-chromosome. Methods include a 3-hour battery of standardized neuropsychological tests to cover a broad range of cognitive domains and to assess major domains of personality. We use magnetic resonance imaging to measure total and regional brain volumes and functional magnetic resonance imaging to measure brain activity while subjects are performing a attention-demanding cognitive task. The genetic testing includes the parental origin of the supernumerary X-chromosome, the pattern of X-chromosome inactivation, androgen receptor (AR) CAGn repeat length, and gene expression profile of brain-expressed genes.

Eligibility criteria: Inclusion Criteria:

* age between 18 and 60 years
* verified KS karyotype (KS patients)

Exclusion Criteria:

* present or past neurological diseases
* present or past head trauma
* contraindication to perform MR scans(Claustrophobia,Magnetic or electric foreign bodies - including cardiac pacemakers, magnetic cerebrovascular clips and electric non-removable appliances dosing medicine)
* extreme adiposity (BMI \> 35 kg/m2)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Medical Department M, Endocrinology and Diabetes, and Medical Research Laboratories, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44
Study officials:
affiliation: Medical Department M, Endocrinology and Diabetes, and Medical Research Laboratories, Clinical Institute, Aarhus University Hospital, Aarhus, Denmark
name: Claus H Gravholt, MD, DMSCI
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Aarhus
name: Anne S Jensen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chang S, Skakkebaek A, Trolle C, Bojesen A, Hertz JM, Cohen A, Hougaard DM, Wallentin M, Pedersen AD, Ostergaard JR, Gravholt CH. Anthropometry in Klinefelter syndrome--multifactorial influences due to CAG length, testosterone treatment and possibly intrauterine hypogonadism. J Clin Endocrinol Metab. 2015 Mar;100(3):E508-17. doi: 10.1210/jc.2014-2834. Epub 2014 Dec 16.
citation: Skakkebaek A, Bojesen A, Kristensen MK, Cohen A, Hougaard DM, Hertz JM, Fedder J, Laurberg P, Wallentin M, Ostergaard JR, Pedersen AD, Gravholt CH. Neuropsychology and brain morphology in Klinefelter syndrome - the impact of genetics. Andrology. 2014 Jul;2(4):632-40. doi: 10.1111/j.2047-2927.2014.00229.x. Epub 2014 May 28.