Trial Outcomes & Findings for Androgen Effect on Klinefelter Syndrome Motor Outcome (NCT NCT00348946)

NCT ID: NCT00348946

Last Updated: 2021-07-08

Results Overview

Outcome measures were tested using the following assessments: Bruininks-Osertesky Test of Motor Proficiency (BOT) subscales of (1) Visual Motor Control, (2) Upper limb Speed, and (3) Strength, Physical and Neurological Evaluation for Soft Signs (PANESS), and Hand Strength Dynamometer. BOT assess the child's motor development and includes standard scores (mean=100, SD=15) and subtest scores and is normed for sex and age (4-14.5 years). PANESS assesses the time required to press thumb to 4 fingers 20 times for the dominant and nondominant hands and includes standard scores (mean=100, SD=15) with age-specific norms (4-18 years). Hand strength dynamometer assess hand strength in the dominant and nondominant hands and includes standard scores (mean=100, SD=15). Data is expressed as standard scores with mean of 100 and SD of 15. The minimum standard score is 50; the maximum standard score is 145. Higher scorers imply better function.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

93 participants

Primary outcome timeframe

2 years per subject

Results posted on

2021-07-08

Participant Flow

Participant milestones

Participant milestones
Measure
Oxandrolone
androgen oxandrolone: Oxandrolone ,0.6 \>mg/kg/day, orally, for 2 years.
Placebo
placebo: an inactive substance
Overall Study
STARTED
46
47
Overall Study
COMPLETED
35
35
Overall Study
NOT COMPLETED
11
12

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Androgen Effect on Klinefelter Syndrome Motor Outcome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Oxandrolone
n=46 Participants
androgen oxandrolone: Oxandrolone ,0.6 \>mg/kg/day, orally, for 2 years.
Placebo
n=47 Participants
placebo: an inactive substance
Total
n=93 Participants
Total of all reporting groups
Age, Categorical
<=18 years
46 Participants
n=5 Participants
47 Participants
n=7 Participants
93 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Continuous
6.9 years
STANDARD_DEVIATION 2.2 • n=5 Participants
8.5 years
STANDARD_DEVIATION 2.6 • n=7 Participants
7.7 years
STANDARD_DEVIATION 2.5 • n=5 Participants
Sex: Female, Male
Female
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Sex: Female, Male
Male
46 Participants
n=5 Participants
47 Participants
n=7 Participants
93 Participants
n=5 Participants
Race/Ethnicity, Customized
Ethnicity · White
33 Participants
n=5 Participants
34 Participants
n=7 Participants
67 Participants
n=5 Participants
Race/Ethnicity, Customized
Ethnicity · African American
6 Participants
n=5 Participants
6 Participants
n=7 Participants
12 Participants
n=5 Participants
Race/Ethnicity, Customized
Ethnicity · Hispanic
5 Participants
n=5 Participants
3 Participants
n=7 Participants
8 Participants
n=5 Participants
Race/Ethnicity, Customized
Ethnicity · Asian/Pacific Islander
2 Participants
n=5 Participants
3 Participants
n=7 Participants
5 Participants
n=5 Participants
Race/Ethnicity, Customized
Ethnicity · Other
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Tanner 1 pubic hair
43 Participants
n=5 Participants
38 Participants
n=7 Participants
81 Participants
n=5 Participants
BMI Standard Deviation Score (SDS)
0.40 kg/m^2
STANDARD_DEVIATION 1.15 • n=5 Participants
0.58 kg/m^2
STANDARD_DEVIATION 1.17 • n=7 Participants
0.49 kg/m^2
STANDARD_DEVIATION 1.16 • n=5 Participants
Waist circumference percentile >75 percentile
17 Participants
n=5 Participants
22 Participants
n=7 Participants
39 Participants
n=5 Participants
Total cholesterol
167 mg/dL
STANDARD_DEVIATION 33 • n=5 Participants
162 mg/dL
STANDARD_DEVIATION 27 • n=7 Participants
164 mg/dL
STANDARD_DEVIATION 29 • n=5 Participants
LDL cholesterol
106 mg/dL
STANDARD_DEVIATION 31 • n=5 Participants
104 mg/dL
STANDARD_DEVIATION 24 • n=7 Participants
104.4 mg/dL
STANDARD_DEVIATION 25.4 • n=5 Participants
Triglycerides
75.4 mg/dL
STANDARD_DEVIATION 58.2 • n=5 Participants
67.7 mg/dL
STANDARD_DEVIATION 32.6 • n=7 Participants
70.7 mg/dL
STANDARD_DEVIATION 46 • n=5 Participants
Triglycerides > 100 mg/dL
9 Participants
n=5 Participants
6 Participants
n=7 Participants
15 Participants
n=5 Participants
HDL cholesterol
46 mg/dL
STANDARD_DEVIATION 10.4 • n=5 Participants
44.8 mg/dL
STANDARD_DEVIATION 10.1 • n=7 Participants
45.7 mg/dL
STANDARD_DEVIATION 10 • n=5 Participants
HDL cholesterol < 50 mg/dL
31 Participants
n=5 Participants
31 Participants
n=7 Participants
62 Participants
n=5 Participants
Fasting blood glucose, mg/dL
84.8 mg/dL
STANDARD_DEVIATION 8.4 • n=5 Participants
85.2 mg/dL
STANDARD_DEVIATION 6.7 • n=7 Participants
85.2 mg/dL
STANDARD_DEVIATION 7.6 • n=5 Participants
Fasting blood glucose > 110 mg/dL
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Systolic blood pressure
87.2 mm Hg
STANDARD_DEVIATION 9.7 • n=5 Participants
90.9 mm Hg
STANDARD_DEVIATION 9.4 • n=7 Participants
88.7 mm Hg
STANDARD_DEVIATION 9.6 • n=5 Participants
Systolic blood pressure > 90th percentile for age and height
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Diastolic blood pressure
52.3 mm Hg
STANDARD_DEVIATION 6.9 • n=5 Participants
56.9 mm Hg
STANDARD_DEVIATION 7.3 • n=7 Participants
55 mm Hg
STANDARD_DEVIATION 8.5 • n=5 Participants
Diastolic blood pressure > 90th percentile for age and height
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 2 years per subject

Population: Some participants were not able to complete all test and/or it was determined by the investigator that their results do reflect their ability and they were removed from the analysis.

Outcome measures were tested using the following assessments: Bruininks-Osertesky Test of Motor Proficiency (BOT) subscales of (1) Visual Motor Control, (2) Upper limb Speed, and (3) Strength, Physical and Neurological Evaluation for Soft Signs (PANESS), and Hand Strength Dynamometer. BOT assess the child's motor development and includes standard scores (mean=100, SD=15) and subtest scores and is normed for sex and age (4-14.5 years). PANESS assesses the time required to press thumb to 4 fingers 20 times for the dominant and nondominant hands and includes standard scores (mean=100, SD=15) with age-specific norms (4-18 years). Hand strength dynamometer assess hand strength in the dominant and nondominant hands and includes standard scores (mean=100, SD=15). Data is expressed as standard scores with mean of 100 and SD of 15. The minimum standard score is 50; the maximum standard score is 145. Higher scorers imply better function.

Outcome measures

Outcome measures
Measure
Oxandrolone
n=35 Participants
androgen oxandrolone: Oxandrolone ,06 \>mg/kg/day, orally, for 2 years
Placebo
n=36 Participants
placebo: an inactive substance
Motor Function/Strength
PANESS SS- dominant hand
91 score on a scale
Standard Deviation 3
91 score on a scale
Standard Deviation 3
Motor Function/Strength
BOT Visual-motor control SS
86 score on a scale
Standard Deviation 1
81 score on a scale
Standard Deviation 1
Motor Function/Strength
BOT Upper limb speed SS
92 score on a scale
Standard Deviation 1
89 score on a scale
Standard Deviation 2
Motor Function/Strength
BOT Strength SS
88 score on a scale
Standard Deviation 1
85 score on a scale
Standard Deviation 1
Motor Function/Strength
Hand Dynamometer SS- dominant hand
123 score on a scale
Standard Deviation 2
118 score on a scale
Standard Deviation 2

SECONDARY outcome

Timeframe: 2 years per subject

Outcome measures were tested using the Differential Ability Scales - 2nd edition (DAS-II). DAS-II provides an age- and sex-standardized assessment of intellectual functioning (General Concept Ability subscale similar to IQ) in children ages 2-17 years of age (mean=100, SD=15). The Verbal Cluster measures the child's ability to define words and perform verbal reasoning tasks. The Nonverbal Cluster measures the child's inductive and sequential reasoning abilities. The Spatial Cluster measures visuospatial construction ability, spatial memory, and spatial reasoning. Data is expressed as standard scores with mean of 100 and SD of 15. The minimum standard score is 50; the maximum standard score is 145. Higher scores imply better function.

Outcome measures

Outcome measures
Measure
Oxandrolone
n=35 Participants
androgen oxandrolone: Oxandrolone ,06 \>mg/kg/day, orally, for 2 years
Placebo
n=36 Participants
placebo: an inactive substance
Cognitive Function and Language
DAS: General Concept Ability
96 score on a scale
Standard Deviation 2
94 score on a scale
Standard Deviation 2
Cognitive Function and Language
DAS: Verbal Cluster
92 score on a scale
Standard Deviation 2
90 score on a scale
Standard Deviation 2
Cognitive Function and Language
DAS: Nonverbal Cluster
102 score on a scale
Standard Deviation 2
101 score on a scale
Standard Deviation 2
Cognitive Function and Language
DAS: Spatial Cluster
96 score on a scale
Standard Deviation 2
94 score on a scale
Standard Deviation 2

SECONDARY outcome

Timeframe: 2 years per participant

Population: Some participants were not able to complete all assessments and/or it was determined by the investigator that their results do reflect their ability and they were removed from the analysis .

Outcome measures were tested using the following cognitive assessments: Digit Span Backward, A Neuropsychological Assessment (NEPSY) subscales of (1) Phonemic Fluency and (2) Semantic Fluency, and Connors' Continuous Performance Test (CPT-II) subscales (1) Omissions, (2) Commissions, (3) Hit Reaction, (4) Variability, and (5) Preservations. Digit Span Backward tests working memory and is normed for children ages 5-16 years. Phonemic Fluency measures the number of words that the child can name beginning with the letters F and S (ages 6-12). Semantic Fluency measures the number of words the child can name in the categories food and drink (ages 4-12). CPT-II measures the ability to maintain attention over an extended period of time. All scores are reported as standard scores with a mean of 100 and SD of 15. The minimum standard score is 50; the maximum standard score is 145. Higher scores imply better function.

Outcome measures

Outcome measures
Measure
Oxandrolone
n=32 Participants
androgen oxandrolone: Oxandrolone ,06 \>mg/kg/day, orally, for 2 years
Placebo
n=33 Participants
placebo: an inactive substance
Working Memory/Attention
Digit span backward
96 score on a scale
Standard Deviation 2
92 score on a scale
Standard Deviation 2
Working Memory/Attention
Phonemic fluency
95 score on a scale
Standard Deviation 3
91 score on a scale
Standard Deviation 2
Working Memory/Attention
Semantic fluency
99 score on a scale
Standard Deviation 4
94 score on a scale
Standard Deviation 3
Working Memory/Attention
CPT: hit reaction time
84 score on a scale
Standard Deviation 3
80 score on a scale
Standard Deviation 3
Working Memory/Attention
CPT: omissions
88 score on a scale
Standard Deviation 4
83 score on a scale
Standard Deviation 4
Working Memory/Attention
CPT: commissions
101 score on a scale
Standard Deviation 2
100 score on a scale
Standard Deviation 2
Working Memory/Attention
CPT variability
86 score on a scale
Standard Deviation 2
86 score on a scale
Standard Deviation 2
Working Memory/Attention
CPT: preservations
76 score on a scale
Standard Deviation 5
74 score on a scale
Standard Deviation 5

SECONDARY outcome

Timeframe: 2 years per participants

Population: Some participants were not able to complete all assessments and/or it was determined by the investigator that their results do reflect their ability and they were removed from the analysis.

Outcome measures were tested using the following social assessments: The Child Behavior Checklist (CBCL) and The Children's Depression Inventory (CDI). The CBCL is standardized measure of behavior problems and social competency normed for children ages 4-16. Higher scores indicate more problems, with the cutoff for the clinical range at a t score greater than or equal to 67. The CDI assess cognitive, affective and behavioral signs of depression in children ages 6-17. The CDI total score reflects the presence of overall depressive symptoms. All scores are expressed as t-scores with a mean of 50 and SD of 10. Lower scores imply better function and higher scores indicate more problem behaviors.

Outcome measures

Outcome measures
Measure
Oxandrolone
n=35 Participants
androgen oxandrolone: Oxandrolone ,06 \>mg/kg/day, orally, for 2 years
Placebo
n=36 Participants
placebo: an inactive substance
Psychosocial and Behavior Domain
CBCL: internalizing total t-score
54 score on a scale
Standard Deviation 1
57 score on a scale
Standard Deviation 1
Psychosocial and Behavior Domain
CBCL: externalizing total t-score
51 score on a scale
Standard Deviation 2
54 score on a scale
Standard Deviation 1
Psychosocial and Behavior Domain
CDI: total t-score
45 score on a scale
Standard Deviation 2
47 score on a scale
Standard Deviation 2
Psychosocial and Behavior Domain
CBCL: behavior total t-score
56 score on a scale
Standard Deviation 1
59 score on a scale
Standard Deviation 1

SECONDARY outcome

Timeframe: 2 years per subject

Outcome measures were tested using The Piers-Harris Self Concept Scale. Scoring provides a total standard score and scores on six subscales: physical appearance and attributes, freedom from anxiety, intellectual and school status, behavioral adjustment, happiness and satisfaction, and popularity. Subscales are summed and standardized to provide the total standard score with a mean of 100 and SD of 15. The minimum standard score is 50; the maximum standard score is 145. Higher scores imply better function.

Outcome measures

Outcome measures
Measure
Oxandrolone
n=16 Participants
androgen oxandrolone: Oxandrolone ,06 \>mg/kg/day, orally, for 2 years
Placebo
n=20 Participants
placebo: an inactive substance
Psychosocial and Behavior Domain
105 units on a scale
Standard Deviation 3
100 units on a scale
Standard Deviation 2

Adverse Events

Oxandrolone

Serious events: 0 serious events
Other events: 36 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 38 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Oxandrolone
n=46 participants at risk
androgen oxandrolone: Oxandrolone ,0.6 \>mg/kg/day, orally, for 2 years
Placebo
n=47 participants at risk
placebo: an inactive substance
Musculoskeletal and connective tissue disorders
Musculoskeletal complaints
63.0%
29/46 • Number of events 54 • Two years
61.7%
29/47 • Number of events 53 • Two years
Infections and infestations
Infections (any)
78.3%
36/46 • Number of events 77 • Two years
80.9%
38/47 • Number of events 77 • Two years
Nervous system disorders
Headache
45.7%
21/46 • Number of events 56 • Two years
46.8%
22/47 • Number of events 42 • Two years
Nervous system disorders
Seizure
2.2%
1/46 • Number of events 1 • Two years
0.00%
0/47 • Two years
Musculoskeletal and connective tissue disorders
Emergency room visits - Musculoskeletal
10.9%
5/46 • Number of events 5 • Two years
4.3%
2/47 • Number of events 2 • Two years
Immune system disorders
Emergency room visits - Asthma/allergy
6.5%
3/46 • Number of events 4 • Two years
0.00%
0/47 • Two years
Gastrointestinal disorders
Emergency room visits - Gastrointestinal
4.3%
2/46 • Number of events 2 • Two years
2.1%
1/47 • Number of events 1 • Two years
Nervous system disorders
Emergency room visits
4.3%
2/46 • Number of events 2 • Two years
2.1%
1/47 • Number of events 1 • Two years
Infections and infestations
Emergency room visits
6.5%
3/46 • Number of events 4 • Two years
6.4%
3/47 • Number of events 3 • Two years
General disorders
Emergency room visits - other
2.2%
1/46 • Number of events 1 • Two years
2.1%
1/47 • Number of events 1 • Two years
General disorders
Hospitalizations - Medical
2.2%
1/46 • Number of events 1 • Two years
2.1%
1/47 • Number of events 1 • Two years
Psychiatric disorders
Hospitalizations - Psychiatric
2.2%
1/46 • Number of events 1 • Two years
2.1%
1/47 • Number of events 1 • Two years

Additional Information

Judith L. Ross, M.D.

Thomas Jefferson University

Phone: 215-955-1648

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place