Graves' Disease
Conditions
Keywords
Graves' disease, Radioactive iodine, Hypothyroidism
Brief summary
The study will try to answer the question of whether early treatment with levothyroxine at 4 weeks after radioactive iodine for Graves'disease will prevent overt hypothyroidism (low thyroid hormone levels).
Interventions
DRUGLevothyroxine
Early initiation of levothyroxine after radioactive iodine (to start at 4 weeks).
OTHERPlacebo
Placebo to start at 4 weeks after RAI
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
-all adult patients (ages 18-70 years) with Graves' Disease (GD) who will receive radioactive iodine (RAI) ablation of the thyroid gland for treatment of GD
Exclusion criteria
* clinically manifest Graves' ophthalmopathy (GO) * recent (\<1 yr.) history of arrhythmias or any history of ventricular arrhythmias * preexistent cardiomyopathy * malnutrition * psychiatric history that could get worse if patient remains persistently hyperthyroid * unlikely to return for the planned follow-up visits * unlikely to comply with the blood drawing schedule * unlikely to complete the hypothyroid-Health Related Quality of Life (HDQL) and Thyroid Specific (TSQ) questionnaires
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overt Hypothyroidism | 8 weeks | Incidence of overt hypothyroidism at 8 weeks post radioactive iodine treatment (RAI). Overt hypothyroidism was defined as thyroid stimulating hormone (TSH) test result \> 3.0 milliunits per liter (mIU/L) or thyroid hormone free T4 (fT4) \< 0.8 nanograms per deciliter (ng/dL). Free T4 is the portion of total T4 thyroid hormone that is available to your tissues in your bloodstream. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hypothyroid-Health Related Quality of Life | 4 weeks, 8 weeks | The mean change in Quality of life scores was measured by the Hypothyroid-Health Related Quality of Life (HRQL) questionnaire. This questionnaire consists of 27 questions specifying the severity of the discomfort or symptoms of hypothyroidism using a 5 point scale for each question with not at all=1 to all the time=5. Higher scores are associated with a lower quality of life. The change between weeks 4 and 8 were assessed using a hierarchical linear model. The primary parameter of interest from the model was the treatment by time interaction term. Time was a collection of indicator values representing each assessment point. |
| Change in Thyroid Specific Quality of Life | 4 weeks, 8 weeks | The mean change in quality of life scores was measured by the Thyroid Specific Questionnaire (TSQ). This questionnaire consists of 12 questions ranked on a four-point scale for each question where 0 is 'better than usual' and 3 is 'much less than usual'. A higher score indicates higher levels of dissatisfaction and a lower quality of life. The change between weeks 4 and 8 were assessed using a hierarchical linear model. The primary parameter of interest from the model was the treatment by time interaction term. Time was a collection of indicator values representing each assessment point. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Levothyroxine In the intervention arm patients will start levothyroxine therapy at 4 weeks after RAI therapy. The initial dose of levothyroxine will be 25 mcg/day. It will be increased to 50 mcg/day 2 weeks later and then adjusted at 8 weeks post RAI based on a full face-to-face clinical and biochemical evaluation.
Levothyroxine: Early initiation of levothyroxine after radioactive iodine (to start at 4 weeks). | 30 |
| Placebo In the control arm patients will receive placebo capsules and be evaluated for levothyroxine therapy during a full face-to-face evaluation at 8 weeks.
Placebo: Placebo to start at 4 weeks after RAI | 31 |
| Total | 61 |
Baseline characteristics
| Characteristic | Levothyroxine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 47 years STANDARD_DEVIATION 15 | 48 years STANDARD_DEVIATION 13 | 47.5 years STANDARD_DEVIATION 14 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 30 participants | 31 participants | 61 participants |
| Sex: Female, Male Female | 23 Participants | 26 Participants | 49 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
| Thyroid size | 32.7 grams STANDARD_DEVIATION 10.8 | 31.4 grams STANDARD_DEVIATION 13.9 | 32 grams STANDARD_DEVIATION 12.3 |
| Weight | 68.5 kg STANDARD_DEVIATION 16.6 | 73.4 kg STANDARD_DEVIATION 17.5 | 70.9 kg STANDARD_DEVIATION 17 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 31 |
| other Total, other adverse events | 3 / 30 | 0 / 31 |
| serious Total, serious adverse events | 1 / 30 | 0 / 31 |
Outcome results
Primary
Number of Participants With Overt Hypothyroidism
Incidence of overt hypothyroidism at 8 weeks post radioactive iodine treatment (RAI). Overt hypothyroidism was defined as thyroid stimulating hormone (TSH) test result \> 3.0 milliunits per liter (mIU/L) or thyroid hormone free T4 (fT4) \< 0.8 nanograms per deciliter (ng/dL). Free T4 is the portion of total T4 thyroid hormone that is available to your tissues in your bloodstream.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Levothyroxine | Number of Participants With Overt Hypothyroidism | 11 Participants |
| Placebo | Number of Participants With Overt Hypothyroidism | 17 Participants |
p-value: 0.23Fisher Exact
Secondary
Change in Hypothyroid-Health Related Quality of Life
The mean change in Quality of life scores was measured by the Hypothyroid-Health Related Quality of Life (HRQL) questionnaire. This questionnaire consists of 27 questions specifying the severity of the discomfort or symptoms of hypothyroidism using a 5 point scale for each question with not at all=1 to all the time=5. Higher scores are associated with a lower quality of life. The change between weeks 4 and 8 were assessed using a hierarchical linear model. The primary parameter of interest from the model was the treatment by time interaction term. Time was a collection of indicator values representing each assessment point.
Time frame: 4 weeks, 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levothyroxine | Change in Hypothyroid-Health Related Quality of Life | 12 units on a scale | Standard Deviation 28.4 |
| Placebo | Change in Hypothyroid-Health Related Quality of Life | 19.8 units on a scale | Standard Deviation 25 |
p-value: 0.41Regression, Linear
Secondary
Change in Thyroid Specific Quality of Life
The mean change in quality of life scores was measured by the Thyroid Specific Questionnaire (TSQ). This questionnaire consists of 12 questions ranked on a four-point scale for each question where 0 is 'better than usual' and 3 is 'much less than usual'. A higher score indicates higher levels of dissatisfaction and a lower quality of life. The change between weeks 4 and 8 were assessed using a hierarchical linear model. The primary parameter of interest from the model was the treatment by time interaction term. Time was a collection of indicator values representing each assessment point.
Time frame: 4 weeks, 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levothyroxine | Change in Thyroid Specific Quality of Life | -2 units on a scale | Standard Deviation 12.8 |
| Placebo | Change in Thyroid Specific Quality of Life | -3.8 units on a scale | Standard Deviation 8.7 |
p-value: 0.33Regression, Linear