Trial Outcomes & Findings for Efficacy Assessment of Systematic Treatment With Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children (NCT NCT01576705)
NCT ID: NCT01576705
Last Updated: 2020-05-13
Results Overview
GMDS for testing and estimate babies psychomotor development from birth to 2 years trough six subscales : Locomotor, Personal-social, Hearing and language, Eye-Hand coordination, Performance.Sub- and General Quotients (GDQ) standard score are based on a mean of 100 and a standard deviation of 16. For children with delayed development, which is the case for children with Down Syndrome, Quotient tables could be not used because sub- and General quotient floors at 50. For each subscale, a raw score was derived from the contributing items. Total raw score was obtained by adding subscale raw scores. Sum of all subscale raw scores was converted into a development age using correspondence table. Subscale and global development quotients were computed by dividing the development age by the chronological age multiplied by 100. For preterm infants, chronological age was corrected taking into account the gestational term. Higher QD's scores show a better psychomotor development outcome
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
175 participants
Primary outcome timeframe
12 months
Results posted on
2020-05-13
Participant Flow
Recruitment period : 2012-2016 First inclusion : 02/04/2012 Last inclusion : 14/12/2016 Location : Institut Jérôme Lejeune
As recruitment was nationwide and patients were included at a single centre, screening and randomisation were performed on the same day to minimise visits to the centre. Eligibility of randomised patients for TSH levels per exclusion criterion #8 was thus confirmed retrospectively, and patients with high TSH levels were discontinued.
Participant milestones
| Measure |
Thyroxin + Folinic Acid
thyroid hormone and folinic acid: thyroid hormone 25microg in tablets folinic acid 5 mg in capsules
|
Thyroxin+Folinic Acid Placebo
thyroid hormone and folinic acid: thyroid hormone 25microg in tablets folinic acid placebo in capsules
|
Thyroxin Placebo+ Folinic Acid
thyroid hormone and folinic acid: thyroid hormone placebo in tablets folinic acid 5 mg in capsules
|
Thyroxin Placebo+ Folinic Acid Placebo
thyroid hormone and folinic acid: thyroid hormone placebo in tablets folinic acid placebo in capsules
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
43
|
45
|
43
|
44
|
|
Overall Study
COMPLETED
|
40
|
37
|
38
|
41
|
|
Overall Study
NOT COMPLETED
|
3
|
8
|
5
|
3
|
Reasons for withdrawal
| Measure |
Thyroxin + Folinic Acid
thyroid hormone and folinic acid: thyroid hormone 25microg in tablets folinic acid 5 mg in capsules
|
Thyroxin+Folinic Acid Placebo
thyroid hormone and folinic acid: thyroid hormone 25microg in tablets folinic acid placebo in capsules
|
Thyroxin Placebo+ Folinic Acid
thyroid hormone and folinic acid: thyroid hormone placebo in tablets folinic acid 5 mg in capsules
|
Thyroxin Placebo+ Folinic Acid Placebo
thyroid hormone and folinic acid: thyroid hormone placebo in tablets folinic acid placebo in capsules
|
|---|---|---|---|---|
|
Overall Study
TSH > 7 mIU/L at baseline
|
3
|
7
|
5
|
3
|
|
Overall Study
invalid ICF
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Thyroxin + Folinic Acid
n=40 Participants
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
Thyroxin+Folinic Acid Placebo
n=37 Participants
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
Thyroxin Placebo+ Folinic Acid
n=38 Participants
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
Thyroxin Placebo+ Folinic Acid Placebo
n=41 Participants
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
Total
n=156 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Customized
Age
|
12.3 months
STANDARD_DEVIATION 3.4 • n=40 Participants
|
12.2 months
STANDARD_DEVIATION 3.8 • n=37 Participants
|
12.3 months
STANDARD_DEVIATION 4 • n=38 Participants
|
12.7 months
STANDARD_DEVIATION 3.3 • n=41 Participants
|
12.37 months
STANDARD_DEVIATION 3.58 • n=156 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=40 Participants
|
16 Participants
n=37 Participants
|
17 Participants
n=38 Participants
|
17 Participants
n=41 Participants
|
67 Participants
n=156 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=40 Participants
|
21 Participants
n=37 Participants
|
21 Participants
n=38 Participants
|
24 Participants
n=41 Participants
|
89 Participants
n=156 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
France
|
40 Participants
n=40 Participants
|
37 Participants
n=37 Participants
|
38 Participants
n=38 Participants
|
41 Participants
n=41 Participants
|
156 Participants
n=156 Participants
|
|
Patient's height at baseline
|
70.86 cm
STANDARD_DEVIATION 3.88 • n=40 Participants
|
71.14 cm
STANDARD_DEVIATION 5.03 • n=37 Participants
|
71.13 cm
STANDARD_DEVIATION 4.15 • n=38 Participants
|
71.68 cm
STANDARD_DEVIATION 4.36 • n=41 Participants
|
71.21 cm
STANDARD_DEVIATION 4.33 • n=156 Participants
|
|
Karyotype %
Free trisomy 21
|
39 Participants
n=40 Participants
|
37 Participants
n=37 Participants
|
38 Participants
n=38 Participants
|
40 Participants
n=41 Participants
|
154 Participants
n=156 Participants
|
|
Karyotype %
Robertsonian translocation
|
1 Participants
n=40 Participants
|
0 Participants
n=37 Participants
|
0 Participants
n=38 Participants
|
1 Participants
n=41 Participants
|
2 Participants
n=156 Participants
|
|
Pregnancy term
|
38.03 weeks of amenorrhea
STANDARD_DEVIATION 1.37 • n=40 Participants
|
38.14 weeks of amenorrhea
STANDARD_DEVIATION 0.98 • n=37 Participants
|
38.29 weeks of amenorrhea
STANDARD_DEVIATION 1.33 • n=38 Participants
|
37.85 weeks of amenorrhea
STANDARD_DEVIATION 0.99 • n=41 Participants
|
38.07 weeks of amenorrhea
STANDARD_DEVIATION 1.18 • n=156 Participants
|
|
Cardiac abnormalities
Isolated hear murmur
|
1 participants
n=40 Participants
|
3 participants
n=37 Participants
|
2 participants
n=38 Participants
|
1 participants
n=41 Participants
|
7 participants
n=156 Participants
|
|
Cardiac abnormalities
Atrioventricular septal defect (AVSD)
|
2 participants
n=40 Participants
|
1 participants
n=37 Participants
|
1 participants
n=38 Participants
|
2 participants
n=41 Participants
|
6 participants
n=156 Participants
|
|
TSH
|
4.3 mIU/L
STANDARD_DEVIATION 1.7 • n=40 Participants
|
4.32 mIU/L
STANDARD_DEVIATION 1.52 • n=37 Participants
|
4.79 mIU/L
STANDARD_DEVIATION 1.23 • n=38 Participants
|
4.45 mIU/L
STANDARD_DEVIATION 1.49 • n=41 Participants
|
4.46 mIU/L
STANDARD_DEVIATION 1.5 • n=156 Participants
|
|
Patient's weight at baseline
|
8.30 Kg
STANDARD_DEVIATION 1.2 • n=40 Participants
|
8.19 Kg
STANDARD_DEVIATION 1.42 • n=37 Participants
|
8.54 Kg
STANDARD_DEVIATION 1.13 • n=38 Participants
|
8.62 Kg
STANDARD_DEVIATION 1.6 • n=41 Participants
|
8.42 Kg
STANDARD_DEVIATION 1.35 • n=156 Participants
|
|
Patient's head circumference at baseline
|
43.5 cm
STANDARD_DEVIATION 1.59 • n=40 Participants
|
43.55 cm
STANDARD_DEVIATION 1.64 • n=37 Participants
|
43.63 cm
STANDARD_DEVIATION 1.55 • n=38 Participants
|
43.82 cm
STANDARD_DEVIATION 1.68 • n=41 Participants
|
43.63 cm
STANDARD_DEVIATION 1.6 • n=156 Participants
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: The main analysis of the primary efficacy endpoint is the adjusted change from baseline in GDQ derived from the Griffith Mental Development Scales (GMDS) at 12 months analysed by ANCOVA adjusted for covariates. Expected Outcome : six points difference in GDQ between any of the three treatment group compared to placebo at 12 months from baseline.
GMDS for testing and estimate babies psychomotor development from birth to 2 years trough six subscales : Locomotor, Personal-social, Hearing and language, Eye-Hand coordination, Performance.Sub- and General Quotients (GDQ) standard score are based on a mean of 100 and a standard deviation of 16. For children with delayed development, which is the case for children with Down Syndrome, Quotient tables could be not used because sub- and General quotient floors at 50. For each subscale, a raw score was derived from the contributing items. Total raw score was obtained by adding subscale raw scores. Sum of all subscale raw scores was converted into a development age using correspondence table. Subscale and global development quotients were computed by dividing the development age by the chronological age multiplied by 100. For preterm infants, chronological age was corrected taking into account the gestational term. Higher QD's scores show a better psychomotor development outcome
Outcome measures
| Measure |
Thyroxin + Folinic Acid
n=38 Participants
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
Thyroxin+Folinic Acid Placebo
n=35 Participants
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
Thyroxin Placebo+ Folinic Acid
n=30 Participants
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
Thyroxin Placebo+ Folinic Acid Placebo
n=41 Participants
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
|---|---|---|---|---|
|
GMDS (Griffiths Mental Development Scale)
|
51.96 developpement quotient
Standard Deviation 7.88
|
51.27 developpement quotient
Standard Deviation 6.48
|
51.66 developpement quotient
Standard Deviation 6.37
|
51.67 developpement quotient
Standard Deviation 8.29
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: The main analysis of the secondary efficacy endpoint of the adjusted change from baseline in the BL-R GDQ at 12 months, analysed by ANCOVA adjusted for covariates, is presented in the mITT population.
BL includes 4 subscales : Locomotor, Coordination, Language, Sociability. Subscale and global developpemental quotients were computed by dividing the developpemental age by the chronological age multiplied by 100. This kind of formula do not give a min-max outcome. Higher QD's scores show a better psychomotor developpement outcome.
Outcome measures
| Measure |
Thyroxin + Folinic Acid
n=38 Participants
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
Thyroxin+Folinic Acid Placebo
n=35 Participants
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
Thyroxin Placebo+ Folinic Acid
n=30 Participants
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
Thyroxin Placebo+ Folinic Acid Placebo
n=40 Participants
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
|---|---|---|---|---|
|
BL (Brunet Lezine Revised Scale)
|
51.18 developpement quotient
Standard Deviation 6.98
|
50.64 developpement quotient
Standard Deviation 7.25
|
51.24 developpement quotient
Standard Deviation 6.46
|
51.36 developpement quotient
Standard Deviation 8.27
|
Adverse Events
Thyroxin+Folinic Acid Placebo
Serious events: 9 serious events
Other events: 0 other events
Deaths: 0 deaths
Thyroxin + Folinic Acid
Serious events: 8 serious events
Other events: 0 other events
Deaths: 1 deaths
Thyroxin Placebo+ Folinic Acid
Serious events: 8 serious events
Other events: 7 other events
Deaths: 0 deaths
Thyroxin Placebo+ Folinic Acid Placebo
Serious events: 5 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Thyroxin+Folinic Acid Placebo
n=44 participants at risk
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
Thyroxin + Folinic Acid
n=43 participants at risk
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
Thyroxin Placebo+ Folinic Acid
n=43 participants at risk
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
Thyroxin Placebo+ Folinic Acid Placebo
n=44 participants at risk
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
|---|---|---|---|---|
|
Infections and infestations
Infections and infestations
|
6.8%
3/44 • Number of events 3 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
9.3%
4/43 • Number of events 4 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
4.7%
2/43 • Number of events 2 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
11.4%
5/44 • Number of events 7 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
|
9.1%
4/44 • Number of events 5 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
9.3%
4/43 • Number of events 6 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
7.0%
3/43 • Number of events 5 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
|
General disorders
General disorders and administration site conditions
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
4.7%
2/43 • Number of events 2 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
2.3%
1/43 • Number of events 1 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders
|
4.5%
2/44 • Number of events 3 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/43 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/43 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
2.3%
1/44 • Number of events 1 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
|
Surgical and medical procedures
Surgical and medical procedures
|
4.5%
2/44 • Number of events 2 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/43 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
2.3%
1/43 • Number of events 1 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
|
Congenital, familial and genetic disorders
Congenital, familial and genetic disorders
|
2.3%
1/44 • Number of events 1 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/43 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/43 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/43 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
2.3%
1/43 • Number of events 1 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm begign, maligant and unspecified
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/43 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
2.3%
1/43 • Number of events 1 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
|
Nervous system disorders
Nervous system disorders
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/43 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
2.3%
1/43 • Number of events 1 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
|
Skin and subcutaneous tissue disorders
Skin and subcutnaeous tissue disorders
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
2.3%
1/43 • Number of events 1 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/43 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
Other adverse events
| Measure |
Thyroxin+Folinic Acid Placebo
n=44 participants at risk
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
Thyroxin + Folinic Acid
n=43 participants at risk
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
Thyroxin Placebo+ Folinic Acid
n=43 participants at risk
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
Thyroxin Placebo+ Folinic Acid Placebo
n=44 participants at risk
thyroid hormone and folinic acid: thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
|
|---|---|---|---|---|
|
Endocrine disorders
Endocrine disorders
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/43 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
11.6%
5/43 • Number of events 5 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms begnin, malignant and unspecified
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/43 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
2.3%
1/43 • Number of events 1 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
|
Nervous system disorders
Nervous system disorders
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/43 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
2.3%
1/43 • Number of events 1 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
0.00%
0/44 • 12 months
safety analysis were performed on all randomised patients receiving at least one dose of study treatment Safety population correspond to 174 subjects
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place