Congenital Hypothyroidism, Hypothyroidism
Conditions
Brief summary
This study compares two different brands of thyroxine (thyroid hormone). Currently, pharmacists may be substituting generic formulations of thyroid hormone without your doctor knowing about this. Although a small difference in thyroid function is not significant in most healthy children, adolescents and adults, in infants and toddlers even a small difference in thyroid function can have important harmful consequences on brain development. The purpose of the present study is to learn whether the difference between brands of thyroid hormone that are currently being substituted is sufficient to cause a difference in thyroid function.
Detailed description
This study is an unblinded, randomized controlled cross-over study, which involves taking 2 different forms of levothyroxine sequentially over a 16 week period. Subjects will have a total of 3 visits over this time period. At the first visit, subjects are randomized to receive either generic (Sandoz) levothyroxine or Synthroid (Abbott) brand of levothyroxine. Blood is drawn for baseline thyroid function studies and other markers which are influenced by thyroid hormone at each visit. The second visit is the cross-over visit, and the final visit is a close-out visit, after which each subject will resume taking their previous formulation of levothyroxine.
Interventions
DRUGBrand Name Levothyroxine (Synthroid)
Randomized crossover study using 8 weeks of brand name levothyroxine (Synthroid, manufactured by Abbott), then 8 weeks of the generic formulation of levothyroxine (manufactured by Sandoz). The dose of medication does not change throughout the duration of the study.
DRUGGeneric formulation of Levothyroxine
Randomized crossover study using 8 weeks of the generic formulation of levothyroxine (manufactured by Abbott, then 8 weeks of brand name levothyroxine (Synthroid, manufactured by Abbott). The dose of medication does not change throughout the duration of the study.
Sponsors
Boston Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 18 Years
Healthy volunteers
Yes
Inclusion criteria
* Age between 3 and 18 years * Diagnosis of Congenital Hypothyroidism with initial TSH \> 100 * Ability to understand directions and follow all instructions
Exclusion criteria
* Not on any drug interfering with absorption of levothyroxine
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Thyroid Stimulating Hormone as Primary Endpoint Measured at Initiation of Study, After 8 Weeks of One Drug, and Then 8 Weeks After the Second Drug. | 3 points over 16 weeks |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited through flyers in the endocrine clinic and letters with opt-out cards to contact. Recruitment started November 2006 and completed ended March 2010.
Pre-assignment details
Subjects' ages had to be between 3-18 years and had a diagnosis of hypothyroidism, either congenital or acquired with an initial TSH of \>100 uIU/mL.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Branded Synthroid 8 weeks, then generic levothyroxine 8 weeks | 13 |
| Group 2 Generic levothyroxine 8 weeks, then branded Synthroid 8 weeks | 18 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | non-compliant | 1 | 0 |
| Overall Study | samples lost | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Group 2 | Group 1 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 18 Participants | 13 Participants | 31 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 10 years STANDARD_DEVIATION 1 | 10 years STANDARD_DEVIATION 1.2 | 10 years STANDARD_DEVIATION 1.1 |
| Region of Enrollment United States | 18 participants | 13 participants | 31 participants |
| Sex: Female, Male Female | 15 Participants | 9 Participants | 24 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 18 |
| other Total, other adverse events | 0 / 13 | 0 / 18 |
| serious Total, serious adverse events | 0 / 13 | 0 / 18 |
Outcome results
Primary
Thyroid Stimulating Hormone as Primary Endpoint Measured at Initiation of Study, After 8 Weeks of One Drug, and Then 8 Weeks After the Second Drug.
Time frame: 3 points over 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 | Thyroid Stimulating Hormone as Primary Endpoint Measured at Initiation of Study, After 8 Weeks of One Drug, and Then 8 Weeks After the Second Drug. | Baseline | 2.455 uIU/mL | Standard Error 1.532 |
| Group 1 | Thyroid Stimulating Hormone as Primary Endpoint Measured at Initiation of Study, After 8 Weeks of One Drug, and Then 8 Weeks After the Second Drug. | After first drug | 0.788 uIU/mL | Standard Error 0.631 |
| Group 1 | Thyroid Stimulating Hormone as Primary Endpoint Measured at Initiation of Study, After 8 Weeks of One Drug, and Then 8 Weeks After the Second Drug. | After second drug | 3.112 uIU/mL | Standard Error 4.983 |
| Group 2 | Thyroid Stimulating Hormone as Primary Endpoint Measured at Initiation of Study, After 8 Weeks of One Drug, and Then 8 Weeks After the Second Drug. | After first drug | 3.053 uIU/mL | Standard Error 1.233 |
| Group 2 | Thyroid Stimulating Hormone as Primary Endpoint Measured at Initiation of Study, After 8 Weeks of One Drug, and Then 8 Weeks After the Second Drug. | Baseline | 2.131 uIU/mL | Standard Error 1.322 |
| Group 2 | Thyroid Stimulating Hormone as Primary Endpoint Measured at Initiation of Study, After 8 Weeks of One Drug, and Then 8 Weeks After the Second Drug. | After second drug | 1.217 uIU/mL | Standard Error 2.832 |