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Trial record 75 of 313 for:    down syndrome

Treatment Trial of Subclinical Hypothyroidism in Down Syndrome

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ClinicalTrials.gov Identifier: NCT01832753
Recruitment Status : Active, not recruiting
First Posted : April 16, 2013
Results First Posted : June 13, 2019
Last Update Posted : June 13, 2019
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Care Provider);   Primary Purpose: Treatment
Conditions Down Syndrome
Subclinical Hypothyroidism
Intervention Drug: Levothyroxine
Enrollment 12
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Immediate Treatment Delayed Treatment Observation Only
Hide Arm/Group Description

Subjects in this group were observed during months 0-6, were randomized to receive levothyroxine during months 6-12, and received levothyroxine as part of the open label phase months 12-18.

All doses were between between 0.5 - 1 mcg/kg/day.

Subjects in this group were observed during months 0-6, were randomized to receive placebo during months 6-12, and received levothyroxine as part of the open label phase months 12-18.

All doses were between between 0.5 - 1 mcg/kg/day.

Subjects in this group partook in the study during the observational phase months 0-6. Subjects in this group were not randomized to either immediate or delayed treatment groups.
Period Title: Observation Phase (Months 0-6)
Started 5 4 3
Completed 5 4 1
Not Completed 0 0 2
Period Title: Randomization Phase (Months 6-12)
Started 5 4 0 [1]
Completed 4 3 0
Not Completed 1 1 0
[1]
1 subject was not randomized as they did not meet inclusion criteria at the end of observation phase
Period Title: Open Label Dose Phase (Months 12-18)
Started 3 3 0
Completed 3 3 0
Not Completed 0 0 0
Arm/Group Title Immediate Treatment Delayed Treatment Observation Only Total
Hide Arm/Group Description

Subjects in this group were observed during months 0-6, were randomized to receive levothyroxine during months 6-12, and received levothyroxine as part of the open label phase months 12-18.

All doses were between between 0.5 - 1 mcg/kg/day.

Subjects in this group were observed during months 0-6, were randomized to receive placebo during months 6-12, and received levothyroxine as part of the open label phase months 12-18.

All doses were between between 0.5 - 1 mcg/kg/day.

Subjects in this group partook in the study during the observational phase months 0-6. Subjects in this group were not randomized to either immediate or delayed treatment groups. Total of all reporting groups
Overall Number of Baseline Participants 5 4 3 12
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 5 participants 4 participants 3 participants 12 participants
12.4
(9.9 to 15.2)
11.6
(8.7 to 14.4)
16.5
(14.7 to 18.6)
14.0
(10.2 to 15.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 4 participants 3 participants 12 participants
Female
4
  80.0%
4
 100.0%
2
  66.7%
10
  83.3%
Male
1
  20.0%
0
   0.0%
1
  33.3%
2
  16.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 4 participants 3 participants 12 participants
Hispanic or Latino
1
  20.0%
0
   0.0%
0
   0.0%
1
   8.3%
Not Hispanic or Latino
4
  80.0%
4
 100.0%
3
 100.0%
11
  91.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 4 participants 3 participants 12 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  20.0%
2
  50.0%
0
   0.0%
3
  25.0%
White
3
  60.0%
2
  50.0%
3
 100.0%
8
  66.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
  20.0%
0
   0.0%
0
   0.0%
1
   8.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 5 participants 4 participants 3 participants 12 participants
5 4 3 12
BMI Percentile  
Median (Inter-Quartile Range)
Unit of measure:  Percentile
Number Analyzed 5 participants 4 participants 3 participants 12 participants
94
(76 to 99)
98
(77 to 99)
98
(76 to 99)
98
(76 to 99)
1.Primary Outcome
Title Change in Lipid Panel From Baseline at 6, 12 and 18 Months.
Hide Description Lipid panel will be measured via fasting blood draw.
Time Frame baseline, 6 months, 12 months & 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
3 of the 12 participants ("Observation Only") were withdrawn prior to randomization due to normal TSH. 1 of the 4 Delayed Treatment group participants self-withdrew before their 12 month visit. 1 of the 5 Immediate Treatment participants withdrew due to elevated TSH at their 12 month visit, 1 and self-withdrew before their 12 month visit.
Arm/Group Title Immediate Treatment Delayed Treatment Observation Only
Hide Arm/Group Description:

Subjects in this group were observed during months 0-6, were randomized to receive levothyroxine during months 6-12, and received levothyroxine as part of the open label phase months 12-18.

All doses were between between 0.5 - 1 mcg/kg/day.

Subjects in this group were observed during months 0-6, were randomized to receive placebo during months 6-12, and received levothyroxine as part of the open label phase months 12-18.

All doses were between between 0.5 - 1 mcg/kg/day.

Subjects in this group partook in the study during the observational phase months 0-6. Subjects in this group were not randomized to either immediate or delayed treatment groups.
Overall Number of Participants Analyzed 5 4 3
Median (Inter-Quartile Range)
Unit of Measure: mg/dL
Baseline Cholesterol (mg/dL) Number Analyzed 5 participants 4 participants 3 participants
160
(145 to 208)
170
(144 to 201)
163
(150 to 201)
6 month Cholesterol (mg/dL) Number Analyzed 5 participants 4 participants 1 participants
172
(159 to 203)
156.5
(133 to 203.5)
226
(226 to 226)
12 month Cholesterol (mg/dL) Number Analyzed 4 participants 3 participants 0 participants
178.5
(147.5 to 215)
172
(149 to 191)
18 month Cholesterol (mg/dL) Number Analyzed 3 participants 3 participants 0 participants
150
(150 to 217)
164
(134 to 214)
Baseline HDL-C (mg/dL) Number Analyzed 5 participants 4 participants 3 participants
44
(38 to 46)
45.5
(40 to 49.5)
43
(32 to 47)
6 month HDL-C (mg/dL) Number Analyzed 5 participants 4 participants 1 participants
35
(32 to 40)
46.5
(42.5 to 50)
48
(48 to 48)
12 month HDL-C (mg/dL) Number Analyzed 4 participants 3 participants 0 participants
42.5
(40.5 to 43)
44
(37 to 50)
18 month HDL-C (mg/dL) Number Analyzed 3 participants 3 participants 0 participants
38
(36 to 42)
47
(43 to 49)
Baseline LDL-C (mg/dL) Number Analyzed 5 participants 4 participants 3 participants
101
(91 to 145)
108
(82.5 to 133.5)
95
(89 to 138)
6 month LDL-C (mg/dL) Number Analyzed 5 participants 4 participants 1 participants
117
(116 to 120)
96.5
(74.5 to 134.5)
161
(161 to 161)
12 month LDL-C (mg/dL) Number Analyzed 4 participants 3 participants 0 participants
111
(88 to 139.5)
101
(96 to 133)
18 month LDL-C (mg/dL) Number Analyzed 3 participants 3 participants 0 participants
90
(90 to 104)
99
(79 to 148)
Baseline nonHDL-C (mg/dL) Number Analyzed 5 participants 4 participants 3 participants
116
(108 to 160)
124.5
(94.5 to 161)
118
(116 to 158)
6 month nonHDL-C (mg/dL) Number Analyzed 5 participants 4 participants 1 participants
134
(132 to 160)
108
(87 to 157)
178
(178 to 178)
12 month nonHDL-C (mg/dL) Number Analyzed 4 participants 3 participants 0 participants
137.5
(107 to 172)
122
(105 to 154)
18 month nonHDL-C (mg/dL) Number Analyzed 3 participants 3 participants 0 participants
112
(108 to 181)
115
(87 to 171)
Basline Triglycerides (mg/dL) Number Analyzed 5 participants 4 participants 3 participants
73
(73 to 84)
88
(61.5 to 137)
117
(98 to 133)
6 month Triglycerides (mg/dL) Number Analyzed 5 participants 4 participants 1 participants
91
(75 to 96)
83
(61 to 116)
84
(84 to 84)
12 month Triglycerides (mg/dL) Number Analyzed 4 participants 3 participants 0 participants
99
(80.5 to 178)
106
(45 to 107)
18 month Triglycerides (mg/dL) Number Analyzed 3 participants 3 participants 0 participants
108
(91 to 383)
82
(38 to 113)
2.Secondary Outcome
Title Change in Quality of Life From Baseline at 6, 12 and 18 Months.
Hide Description Questionnaires will be done with participants and parents on the day of each study visit to determine body image and quality of life.
Time Frame baseline, 6 months, 12 months, & 18 months
Outcome Measure Data Not Reported
Time Frame Adverse Events were collected throughout the course of the study at each study visit and weekly following randomization up to 18 months.
Adverse Event Reporting Description Adverse Events are tracked over groups divided by phase of study for the purpose of full transparency of the relationship between study drug and AEs.
 
Arm/Group Title Observation Phase Randomization Phase - Placebo Randomization Phase - Treatment Open Label Treatment Phase
Hide Arm/Group Description

Months 0-6

Subjects will be observed for the first 6 months of the study to ensure that the subclinical hypothyroidism is persistent. Subjects who do not have SCH at 6 months will not proceed to the treatment phase.

Subjects that have TSH >10 mIU/L during the 6 month Observational Phase will not be considered subclinical and will not qualify to continue the study. They will be referred to an endocrinologist for treatment.

Months 6-12

This group includes those 4 out of 12 participants that were randomized to the delayed treatment group and received placebo for months 6-12. Adverse events will be reported in this column of the table if the AEs occurred during the phase in which participants were receiving placebo.

Months 6-12

This group includes those 5 of 12 participants that were randomized to immediate treatment. Levothyroxine dose is between 0.5 - 1 mcg/kg/day. There is 1 blood draw visit at month 7.5 (6 weeks after randomization) and 1 study visit at month 12 that will provide the opportunity for dose adjustments if needed.

From months 12-18, all subjects will receive levothyroxine. Levothyroxine dose will be between 0.5 - 1 mcg/kg/day. There will be one blood draw visit at month 13.5 that will provide the opportunity for dose adjustments if needed.

Months 12-18

6 of the starting 12 participants took part in this phase of the study; 3 from the delayed treatment aka placebo group, 3 from the immediate treatment group. From months 12-18, all subjects receive levothyroxine. Levothyroxine dose is between 0.5 - 1 mcg/kg/day. There is one blood draw visit at month 13.5 that will provide the opportunity for dose adjustments if needed.

All-Cause Mortality
Observation Phase Randomization Phase - Placebo Randomization Phase - Treatment Open Label Treatment Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/12 (0.00%)      0/4 (0.00%)      0/5 (0.00%)      0/6 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Observation Phase Randomization Phase - Placebo Randomization Phase - Treatment Open Label Treatment Phase
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/12 (0.00%)      0/4 (0.00%)      0/5 (0.00%)      0/6 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Observation Phase Randomization Phase - Placebo Randomization Phase - Treatment Open Label Treatment Phase
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/12 (8.33%)      4/4 (100.00%)      4/5 (80.00%)      1/6 (16.67%)    
Cardiac disorders         
Racing Heart  [1]  0/12 (0.00%)  0 0/4 (0.00%)  0 1/5 (20.00%)  1 0/6 (0.00%)  0
Gastrointestinal disorders         
Diarrhea  [2]  1/12 (8.33%)  1 2/4 (50.00%)  2 1/5 (20.00%)  1 0/6 (0.00%)  0
General disorders         
Dry mouth  [3]  0/12 (0.00%)  0 1/4 (25.00%)  3 0/5 (0.00%)  0 0/6 (0.00%)  0
Sleeplessness  [4]  0/12 (0.00%)  0 0/4 (0.00%)  0 1/5 (20.00%)  1 1/6 (16.67%)  1
Tired  [5]  0/12 (0.00%)  0 0/4 (0.00%)  0 1/5 (20.00%)  1 0/6 (0.00%)  0
Psychiatric disorders         
Anxiety Symptoms  [6]  0/12 (0.00%)  0 0/4 (0.00%)  0 1/5 (20.00%)  1 0/6 (0.00%)  0
Skin and subcutaneous tissue disorders         
Skin irritation  [7]  0/12 (0.00%)  0 1/4 (25.00%)  1 0/5 (0.00%)  0 0/6 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Racing Heart, Light Headedness, possibly related
[2]
unlikely related
[3]
Chapped lips, dry mouth, unlikely related to study
[4]
not sleeping through the night, restless, irritable, unlikely related to study
[5]
possibly related to study, followed up with TSH/T4 check
[6]
hair pulling & difficulty urinating, unlikely related to study
[7]
Rash on back, unlikely related to study, resolved without intervention
This was a pilot and feasibility study. The number of children with Down syndrome who had elevated TSH (5-10 IU/mL) and who were not on thyroid hormone replacement limited our ability to recruit.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Andrea Kelly, MD MSCE
Organization: The Children's Hospital of Philadelphia
Phone: 215-590-3174 ext 43174
Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT01832753     History of Changes
Other Study ID Numbers: 12-009578
1R01HD071981-01A1 ( U.S. NIH Grant/Contract )
First Submitted: April 9, 2013
First Posted: April 16, 2013
Results First Submitted: November 19, 2018
Results First Posted: June 13, 2019
Last Update Posted: June 13, 2019