Early Levothyroxine Post Radioactive Iodine

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT01950260
• Collaborator: (none)
• Enrollment: 61
• Location: 1
• Arms: 2
• Actual Duration (Months): 43
• Patients Per Site Per Month: 1.4

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Graves' Disease	Drug: Levothyroxine; Other: Placebo	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Prevention of Overt Hypothyroidism Following Radioactive Iodine Therapy for Graves' Disease
• Actual Study Start Date: Sep 1, 2013
• Actual Primary Completion Date: Apr 1, 2017
• Actual Study Completion Date: Apr 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Levothyroxine; Early initiation of levothyroxine after radioactive iodine (to start at 4 weeks).; Other Names: Thyroid hormone
Placebo Comparator: 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.	Other: Placebo; Placebo to start at 4 weeks after RAI

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic

Investigators

• Principal Investigator: Marius Stan, MD, Mayo Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 12, 2015

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• Responsible Party: Marius Stan, Associate Professor of Medicine, Endocrinology Consultant, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01950260
• Other Study ID Numbers: 13-002570
• First Posted: Sep 25, 2013
• Last Update Posted: Oct 29, 2019
• Last Verified: Oct 1, 2019

• Keywords provided by Marius Stan, Associate Professor of Medicine, Endocrinology Consultant, Mayo Clinic: Graves' disease; Radioactive iodine; Hypothyroidism
• Additional relevant MeSH terms: Graves Disease; Hormones

Study Results

Participant Flow

Arm/Group Title	Levothyroxine	Placebo
Arm/Group Description	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).	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
Period Title: Overall Study
STARTED	30	31
COMPLETED	30	31
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Levothyroxine	Placebo	Total
Arm/Group Description	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).	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	Total of all reporting groups
Overall Participants	30	31	61
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47 (15)	48 (13)	47.5 (14)
Sex: Female, Male (Count of Participants)
Female	23 76.7%	26 83.9%	49 80.3%
Male	7 23.3%	5 16.1%	12 19.7%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	30 100%	31 100%	61 100%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	68.5 (16.6)	73.4 (17.5)	70.9 (17)
Thyroid size (grams) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [grams]	32.7 (10.8)	31.4 (13.9)	32 (12.3)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Overt Hypothyroidism
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levothyroxine	Placebo
Arm/Group Description	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).	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
Measure Participants	30	31
Count of Participants [Participants]	11 36.7%	17 54.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levothyroxine, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Change in Hypothyroid-Health Related Quality of Life
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levothyroxine	Placebo
Arm/Group Description	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).	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
Measure Participants	30	31
Mean (Standard Deviation) [units on a scale]	12 (28.4)	19.8 (25.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levothyroxine, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.41
	Comments
	Method	Regression, Linear
	Comments

3. Secondary Outcome

Title	Change in Thyroid Specific Quality of Life
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levothyroxine	Placebo
Arm/Group Description	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).	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
Measure Participants	30	31
Mean (Standard Deviation) [units on a scale]	-2 (12.8)	-3.8 (8.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levothyroxine, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments
	Method	Regression, Linear
	Comments

Adverse Events

Time Frame	Adverse events were collected for each subject from enrollment until study completion, approximately 6 months.
Arm/Group Title	Levothyroxine		Placebo
Arm/Group Description	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).		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
All Cause Mortality
	Levothyroxine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/31 (0%)
Serious Adverse Events
	Levothyroxine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)		0/31 (0%)
Cardiac disorders
Atrial fibrillation	1/30 (3.3%)	1	0/31 (0%)	0
Other (Not Including Serious) Adverse Events
	Levothyroxine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/30 (10%)		0/31 (0%)
Cardiac disorders
Palpitations	3/30 (10%)	3	0/31 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.