- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03325647
TESTO: Testosterone Effects on Short-Term Outcomes in Infants With XXY (TESTO)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
XXY (also known as Klinefelter syndrome) is the most common chromosomal abnormality in males, affecting 1/600 boys. The extra X chromosome leads to insufficient development of the testicles and subsequent testosterone deficiency. Males with XXY also have a high risk for developmental delays, learning disabilities, and cardiovascular disease. An essential question is how much of this risk is because of testosterone deficiency and could therefore be reduced by testosterone supplementation, particularly during critical periods of development.
In typical male development, there is a surge of testosterone in the first few months of life, commonly known as the "mini-puberty period of infancy." This testosterone surge may be critical for neurodevelopmental and cardiometabolic programming throughout life. Recently there has been increased off-label use of testosterone in infants with XXY, however neither the short or long term safety or efficacy have been evaluated. This study aims to quantify the short term effects of testosterone treatment in infants with XXY on neurodevelopment, growth, body composition, testicular function, and safety parameters. This is a double blind randomized placebo controlled trial of testosterone injections 25 mg every 4 weeks for 3 doses in boys with XXY enrolled between 1 and 3 months of age. Outcomes including body fat percentage, scaled motor developmental scores, growth velocity, testicular hormone concentrations, specific metabolites, and safety parameters will be assessed 12 weeks into the study. The groups will then cross-over (all subjects will receive testosterone during the study period) and the outcomes will be reassessed 24 weeks into the study. The secondary questions the investigators will answer with this cross-over is 1) whether benefits in the treatment group at 12 weeks are sustained at 24 weeks, and 2) whether the same benefits are seen if treated after the mini-puberty period.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Colorado
-
Aurora, Colorado, United States, 80045
- Children's Hospital Colorado
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male infants with 47,XXY karyotype identified prenatally who are 4-12 weeks old (31 to 90 days of age). 47,XXY must be from a diagnostic test such as Chorionic Villus Sampling (CVS), amniocentesis, or post-natal blood/tissue. Non-invasive prenatal screening results alone will not be accepted.
Exclusion Criteria:
- >20 percent mosaicism for a normal cell line
- Gestational age at birth <36 weeks
- Birth weight <2.5th percentile or >97.5 percentile for age (small or large for gestational age)
- History of thrombosis in self or a first degree relative
- Exposure to androgen therapy outside the study protocol
- Use of medications known to affect body composition, such as growth hormone or insulin
- Known allergy to the testosterone cypionate solution components including benzyl benzoate, benzyl alcohol, or cottonseed oil
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Visit 1 Drug, Visit 2 Placebo
Subjects in this group will be randomized to receive Testosterone Cypionate 200 Milligram/Milliliter Injectable Solution every 4 weeks x 3 doses, beginning at visit 1, and Placebo Injectable Saline beginning at visit 2.
|
Subjects in one arm will be randomized to receive testosterone cypionate 200 mg/ml intramuscularly every 4 weeks for a total of three doses after visit 1, and receive placebo injectable saline for the same duration starting at visit 2. Subjects in the other arm will be randomized to receive placebo injectable saline every 4 weeks for a total of 3 doses after visit 1, and testosterone cypionate 200 mg/ml intramuscularly for the same duration starting at visit 2.
Subjects in one arm will be randomized to receive testosterone cypionate 200 mg/ml intramuscularly every 4 weeks for a total of three doses after visit 1, and receive placebo injectable saline for the same duration starting at visit 2. Subjects in the other arm will be randomized to receive placebo injectable saline every 4 weeks for a total of 3 doses after visit 1, and testosterone cypionate 200 mg/ml intramuscularly for the same duration starting at visit 2.
|
Experimental: Visit 1 Placebo, Visit 2 Drug
Subjects in this group will be randomized to receive Placebo Injectable Saline beginning at visit 1, and Testosterone Cypionate 200 Milligram/Milliliter Injectable Solution every 4 weeks x 3 doses beginning at visit 2.
|
Subjects in one arm will be randomized to receive testosterone cypionate 200 mg/ml intramuscularly every 4 weeks for a total of three doses after visit 1, and receive placebo injectable saline for the same duration starting at visit 2. Subjects in the other arm will be randomized to receive placebo injectable saline every 4 weeks for a total of 3 doses after visit 1, and testosterone cypionate 200 mg/ml intramuscularly for the same duration starting at visit 2.
Subjects in one arm will be randomized to receive testosterone cypionate 200 mg/ml intramuscularly every 4 weeks for a total of three doses after visit 1, and receive placebo injectable saline for the same duration starting at visit 2. Subjects in the other arm will be randomized to receive placebo injectable saline every 4 weeks for a total of 3 doses after visit 1, and testosterone cypionate 200 mg/ml intramuscularly for the same duration starting at visit 2.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Body Fat Percentage
Time Frame: Baseline and 3 months
|
Body fat percentage will be measured using air displacement plethysmography (PEA POD) at the beginning and end of the study period
|
Baseline and 3 months
|
Change in Composite Motor Score on Alberta Infant Motor Scale
Time Frame: 3 months
|
Motor development will be assessed using the standardized Alberta Infant Motor Scale
|
3 months
|
Change in C14:1 Long Chain Acylcarnitines (LCAC) through targeted metabolomics
Time Frame: Baseline and 3 months
|
Plasma will be processed and stored until batch analysis using electrospray tandem mass spectroscopy per standard protocols to quantify acylcarnitines (short, medium, and long-chain) and Branched-Chain Amino Acids (BCAA--leucine/isoleucine and valine) at baseline and 12 weeks.
|
Baseline and 3 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in height
Time Frame: 6 months
|
Physical exam measurements will be measured by a physician at each visit
|
6 months
|
Change in weight
Time Frame: 6 months
|
Physical exam measurements will be measured by a physician at each visit
|
6 months
|
Change in weight-for-length
Time Frame: 6 months
|
Physical exam measurements will be measured by a physician at each visit
|
6 months
|
Change in waist circumference
Time Frame: 6 months
|
Physical exam measurements will be measured by a physician at each visit
|
6 months
|
Change in serum leptin
Time Frame: 6 months
|
Serum will be collected and measured at each study visit.
|
6 months
|
Change in lipids
Time Frame: 6 months
|
Serum will be collected and measured at each study visit.
|
6 months
|
Change in insulin
Time Frame: 6 months
|
Serum will be collected and measured at each study visit.
|
6 months
|
Change in serum Luteinizing Hormone (LH)
Time Frame: 6 months
|
Serum will be collected at each study visit.
Ultrasensitive LH will be measured.
|
6 months
|
Change in serum Follicle Stimulating Hormone (FSH)
Time Frame: 6 months
|
Serum will be collected at each study visit.
Follicle Stimulating Hormone (FSH) will be measured.
|
6 months
|
Change in Inhibin B (INHB)
Time Frame: 6 months
|
Inhibin B levels will be measured.
|
6 months
|
Change in Anti-Mullerian Hormone (AMH)
Time Frame: 6 months
|
Serum will be collected at each study visit.
AMH levels will be measured.
|
6 months
|
Change in Total Testosterone (Total T)
Time Frame: 6 months
|
Serum will be collected at each study visit.
Total testosterone by mass spectroscopy will be measured.
|
6 months
|
Change in Gross Motor Scores on the Peabody Developmental Motor Scales 2
Time Frame: 6 months
|
Gross motor development will be assessed using the standardized Peabody Developmental Motor Scales 2. The Peabody Developmental Motor Scales 2 measures gross motor development using the subscale of the Gross Motor Quotient, which measures the ability to utilize the large muscle systems.
High scores on this composite are made by children with well-developed gross motor abilities.
|
6 months
|
Change in Gross Motor Scores on the Alberta Infant Motor Scales
Time Frame: 6 months
|
Gross motor development will be assessed using the standardized Alberta Infant Motor Scales (AIMS).
The Alberta Infant Motor Scales is a performance-based and norm-referenced measure of infant gross motor maturation from birth to 18 months.
The AIMS total score is calculated by summing the scores for the 58 items, with the score ranging between 0 and 58.
Higher scores indicate more mature motor development.
The infant's score can then be converted to a percentile and compared with age-equivalent peers from the normative sample.
|
6 months
|
Change in Fine Motor Scores
Time Frame: 6 months
|
Fine motor development will be assessed using the standardized Peabody Developmental Motor Scales 2. The Peabody Developmental Motor Scales 2 measures fine motor development using subscale of the Fine Motor Quotient, which measures a child's ability to use his or her hands and arms to grasp objects, stack blocks, draw figures, and manipulate objects.
High scores on this composite are made by children with well-developed fine motor abilities.
|
6 months
|
Change in Cognitive and Language Composite Scores on the Bayley III
Time Frame: 6 months
|
Cognition and language will be assessed by a trained administrator of developmental tests using the standardized Bayley Scales of Infant and Toddler Development III: cognitive and language domains.
In each subscale, age-standardized scores are calculated using test norms.
Developmental delay is determined by calculating how many standard deviations a child scores from the mean in that subscale.
Typically, the more standard deviations below the mean, the more severe the delay.
|
6 months
|
Change in Adaptive Functioning
Time Frame: 6 months
|
Adaptive Functioning will be assessed using the Adaptive Behavior Assessment System, 3rd edition, completed by the parent about their child.
|
6 months
|
Change in Number and Type of Adverse Events
Time Frame: 6 months
|
Adverse events will be measured by verbal questionnaire and parent-report, to determine safety.
|
6 months
|
Change in Serum BCAA, other LCAC
Time Frame: 6 months
|
BCAA and other LCAC will be measured through targeted metabolomics from serum collection at each visit.
|
6 months
|
Change in Pathway analysis
Time Frame: 3 months
|
Serum Pathways will be measured through untargeted/unbiased metabolomics
|
3 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Shanlee M Davis, MD, University of Colorado, Denver
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Endocrine System Diseases
- Gonadal Disorders
- Disorders of Sex Development
- Urogenital Abnormalities
- Congenital Abnormalities
- Genetic Diseases, Inborn
- Chromosome Disorders
- Sex Chromosome Disorders
- Sex Chromosome Disorders of Sex Development
- Hypogonadism
- Klinefelter Syndrome
- Physiological Effects of Drugs
- Antineoplastic Agents
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Androgens
- Anabolic Agents
- Testosterone
- Methyltestosterone
- Testosterone undecanoate
- Testosterone enanthate
- Testosterone 17 beta-cypionate
Other Study ID Numbers
- 17-1317
- 5K23HD092588-02 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Klinefelter Syndrome
-
University Hospital MuensterCompletedKlinefelter Syndrome, Hypogonadism
-
Lenetix Medical Screening LaboratoryUnknownDown Syndrome (Trisomy 21) | Edward's Syndrome (Trisomy 18) | Patau Syndrome (Trisomy 13) | Klinefelter Syndrome (47, XXY) | and Other Chromosome | Abnormalities.United States
-
University of Colorado, DenverNational Institute of Neurological Disorders and Stroke (NINDS); Children's... and other collaboratorsCompletedKlinefelter Syndrome | XXY SyndromeUnited States
-
Hospices Civils de LyonCompletedKlinefelter SyndromeFrance
-
University of PittsburghTerminated
-
Odense University HospitalAarhus University Hospital; University of CopenhagenCompleted
-
University of Colorado, DenverRecruitingKlinefelter Syndrome | Trisomy X | XYY Syndrome | XXXY and XXXXY Syndrome | Xxyy Syndrome | Xyyy Syndrome | Xxxx Syndrome | Xxxxx Syndrome | Xxxyy Syndrome | Xxyyy Syndrome | Xyyyy Syndrome | Male With Sex Chromosome MosaicismUnited States
-
Thomas Jefferson UniversityNational Institute of Neurological Disorders and Stroke (NINDS)Completed
-
University of Colorado, DenverCompletedKlinefelter SyndromeUnited States
Clinical Trials on Testosterone Cypionate 200 Milligram/Milliliter Injectable Solution
-
St Vincent's Hospital, SydneyRecruitingCastration-resistant Prostate Cancer | Homologous Recombination DeficiencyAustralia
-
University of MiamiAcerus Pharmaceuticals CorporationCompletedHypogonadism, MaleUnited States
-
Eli Lilly and CompanyCompletedHypogonadismUnited States, Germany, Canada, Spain, Korea, Republic of, United Kingdom, Puerto Rico, Italy, Argentina
-
University of RochesterCompletedFacioscapulohumeral Muscular DystrophyUnited States
-
Endo PharmaceuticalsCompletedHypogonadotropic Hypogonadism | Hypogonadism | Hypogonadism, MaleUnited States
-
Eli Lilly and CompanyCompleted
-
Clarus Therapeutics, Inc.Syneos HealthCompletedHypogonadismUnited States
-
Academisch Medisch Centrum - Universiteit van Amsterdam...Radboud University Medical Center; Universitaire Ziekenhuizen KU Leuven; University... and other collaboratorsRecruitingLiver Diseases | Hepatic Encephalopathy | Portal Hypertension | Cirrhosis, Liver | Pathological ProcessesNetherlands, Belgium
-
ORA, Inc.CompletedMeibomian Gland DysfunctionUnited States
-
Florida Orthopaedic InstituteOrthopaedic Trauma AssociationUnknownDeep Vein Thrombosis | Venous ThromboembolismUnited States