Levothyroxine Replacement With Liquid Gel Capsules vs Tablets Post-thyroidectomy
Study Details
Study Description
Brief Summary
In some patients, levothyroxine liquid gel capsules may demonstrate superior absorption than the tablet option. Impaired absorption of thyroid hormone directly correlates to higher and more unpredictable TSH (thyroid stimulating hormone) levels.
The investigators therefore hypothesize that following thyroidectomy for Stage I/II differentiated thyroid cancer the gel capsule levothyroxine formulation will provide more predictable TSH results and in turn require fewer dose adjustments to achieve optimal hormone levels in the postoperative period.
The aim of this investigation is to compare the use of levothyroxine in liquid gel capsules to tablet form for TSH suppression following thyroidectomy for presumed stage I/II differentiated thyroid cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
Ten patients will be randomized prior to surgery to receive levothyroxine in tablet form and ten patients will be randomized to receive in gel capsule form. Both forms will be encapsulated in order to allow double-blinding of the study.
The postoperative goal TSH will be between 0.1 and 0.5 mU/L (milli units per litre) in both arms.
Patients will be seen at weeks 6, 12 and 18 postoperatively and have TSH and Free T4 measured. The primary outcome is the number of patients at each visit that are at goal range TSH.
A secondary analysis will compare the dose changes required between the two groups in order to achieve goal TSH.
Another secondary analysis will investigate the patients' quality of life. Two different surveys (see secondary outcomes below) will be performed at both study entry and completion to compare the two groups.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Tablets Patients in this arm will receive levothyroxine tablets (encapsulated for blinding purposes) |
Drug: Levothyroxine
Patients post-thyroidectomy will receive either levothyroxine in tablet form or in gelcaps. Initial dose 1.5-1.8 mcg per kg, orally and daily
Other Names:
|
| Experimental: Gelcaps Patients in this arm will receive levothyroxine gelcaps (encapsulated for blinding purposes) |
Drug: Levothyroxine
Patients post-thyroidectomy will receive either levothyroxine in tablet form or in gelcaps. Initial dose 1.5-1.8 mcg per kg, orally and daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Patients in Each Group at Predefined Target TSH Range at 18 Weeks [18 weeks]
The target TSH (Thyroid stimulating hormone) range will be 0.1 to 0.5 mU/L. The number of patients in each arm (gelcaps or tablets) who are in this range at the completion of the study (18 weeks) will be assessed and the data compared at completion of the study.
Secondary Outcome Measures
- Mean Number of Dose Adjustments [18 weeks]
The number of dose adjustments required to attain TSH target range for each formulation will be tabulated and the data compared at the end of the study
- Change in Mean Patient Quality of Life Score [Baseline,18 weeks]
Patients will be administered survey (Thyroid-Dependent Quality of Life ) to assess their quality of life (at the beginning of the study and again at study completion). The results of these scores will be tabulated and compared between the two arms. Possible score range from 0 to 450; lower score means improved quality of life.
- Treatment Satisfaction Survey [18 weeks]
The Thyroid Treatment Satisfaction Questionnaire Measures the treatment satisfaction. Possible measure 0 to 42; Higher the score, better the outcome (more satisfied the patient)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age > 18 years
-
Presumed AJCC (American Joint Committee on Cancer) tumor Stage I or II
-
Planned total or near-total thyroidectomy
-
Planned goal TSH suppression 0.1-0.5 mU/L for at least 18 weeks postoperatively
-
Normal serum TSH within 12 months preceding surgery
Exclusion Criteria:
-
AJCC Stage III or greater
-
Undifferentiated, Anaplastic or Medullary Thyroid Cancer
-
Planned postoperative TSH goal other than 0.1-0.5 mU/L
-
History of gastrointestinal malabsorption or gastric bypass surgery
-
Pregnancy
-
Use of medications that alter the absorption or metabolism of levothyroxine
-
Prior use of levothyroxine
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Texas Southwestern Medical Center | Dallas | Texas | United States | 75390 |
Sponsors and Collaborators
- University of Texas Southwestern Medical Center
- Akrimax Pharmaceuticals
Investigators
- Principal Investigator: Alex Tessnow, MD, University of Texas Southwestern Medical Center
Study Documents (Full-Text)
More Information
Publications
- McMillan CV, Bradley C, Woodcock A, Razvi S, Weaver JU. Design of new questionnaires to measure quality of life and treatment satisfaction in hypothyroidism. Thyroid. 2004 Nov;14(11):916-25.
- Vita R, Fallahi P, Antonelli A, Benvenga S. The administration of L-thyroxine as soft gel capsule or liquid solution. Expert Opin Drug Deliv. 2014 Jul;11(7):1103-11. doi: 10.1517/17425247.2014.918101. Epub 2014 Jun 4. Review.
- STU 022015-044
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Tablets | Gelcaps |
|---|---|---|
| Arm/Group Description | Patients in this arm will receive levothyroxine tablets (encapsulated for blinding purposes) Levothyroxine: Patients post-thyroidectomy will receive either levothyroxine in tablet form or in gelcaps | Patients in this arm will receive levothyroxine gelcaps (encapsulated for blinding purposes) Levothyroxine: Patients post-thyroidectomy will receive either levothyroxine in tablet form or in gelcaps |
| Period Title: Overall Study | ||
| STARTED | 6 | 8 |
| COMPLETED | 5 | 5 |
| NOT COMPLETED | 1 | 3 |
Baseline Characteristics
| Arm/Group Title | Tablets | Gelcaps | Total |
|---|---|---|---|
| Arm/Group Description | Patients in this arm will receive levothyroxine tablets (encapsulated for blinding purposes) Levothyroxine: Patients post-thyroidectomy will receive either levothyroxine in tablet form or in gelcaps | Patients in this arm will receive levothyroxine gelcaps (encapsulated for blinding purposes) Levothyroxine: Patients post-thyroidectomy will receive either levothyroxine in tablet form or in gelcaps | Total of all reporting groups |
| Overall Participants | 6 | 8 | 14 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
5
83.3%
|
7
87.5%
|
12
85.7%
|
| >=65 years |
1
16.7%
|
1
12.5%
|
2
14.3%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
3
50%
|
7
87.5%
|
10
71.4%
|
| Male |
3
50%
|
1
12.5%
|
4
28.6%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
12.5%
|
1
7.1%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
16.7%
|
0
0%
|
1
7.1%
|
| White |
5
83.3%
|
7
87.5%
|
12
85.7%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Number of Patients in Each Group at Predefined Target TSH Range at 18 Weeks |
|---|---|
| Description | The target TSH (Thyroid stimulating hormone) range will be 0.1 to 0.5 mU/L. The number of patients in each arm (gelcaps or tablets) who are in this range at the completion of the study (18 weeks) will be assessed and the data compared at completion of the study. |
| Time Frame | 18 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tablets | Gelcaps |
|---|---|---|
| Arm/Group Description | Patients in this arm will receive levothyroxine tablets (encapsulated for blinding purposes) Levothyroxine: Patients post-thyroidectomy will receive either levothyroxine in tablet form or in gelcaps | Patients in this arm will receive levothyroxine gelcaps (encapsulated for blinding purposes) Levothyroxine: Patients post-thyroidectomy will receive either levothyroxine in tablet form or in gelcaps |
| Measure Participants | 6 | 8 |
| Count of Participants [Participants] |
2
33.3%
|
4
50%
|
| Title | Mean Number of Dose Adjustments |
|---|---|
| Description | The number of dose adjustments required to attain TSH target range for each formulation will be tabulated and the data compared at the end of the study |
| Time Frame | 18 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tablets | Gelcaps |
|---|---|---|
| Arm/Group Description | Patients in this arm will receive levothyroxine tablets (encapsulated for blinding purposes) Levothyroxine: Patients post-thyroidectomy will receive either levothyroxine in tablet form or in gelcaps | Patients in this arm will receive levothyroxine gelcaps (encapsulated for blinding purposes) Levothyroxine: Patients post-thyroidectomy will receive either levothyroxine in tablet form or in gelcaps |
| Measure Participants | 6 | 8 |
| Mean (Standard Deviation) [The number of dose adjustments] |
2.0
(0.63)
|
1.25
(1.04)
|
| Title | Change in Mean Patient Quality of Life Score |
|---|---|
| Description | Patients will be administered survey (Thyroid-Dependent Quality of Life ) to assess their quality of life (at the beginning of the study and again at study completion). The results of these scores will be tabulated and compared between the two arms. Possible score range from 0 to 450; lower score means improved quality of life. |
| Time Frame | Baseline,18 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Out of 6 people from the Tablet group, 1 did not complete the second survey. Out of 8 people from the Gelcap group, 3 people did not complete the survey. |
| Arm/Group Title | Tablets | Gelcaps |
|---|---|---|
| Arm/Group Description | Patients in this arm will receive levothyroxine tablets (encapsulated for blinding purposes) Levothyroxine: Patients post-thyroidectomy will receive either levothyroxine in tablet form or in gelcaps | Patients in this arm will receive levothyroxine gelcaps (encapsulated for blinding purposes) Levothyroxine: Patients post-thyroidectomy will receive either levothyroxine in tablet form or in gelcaps |
| Measure Participants | 5 | 5 |
| Mean (Standard Deviation) [score on a scale] |
-1.2
(12.99)
|
-29.6
(48.06)
|
| Title | Treatment Satisfaction Survey |
|---|---|
| Description | The Thyroid Treatment Satisfaction Questionnaire Measures the treatment satisfaction. Possible measure 0 to 42; Higher the score, better the outcome (more satisfied the patient) |
| Time Frame | 18 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Out of 6 people from the Tablet group, 1 did not complete the second survey. Out of 8 people from the Gelcap group, 3 people did not complete the survey. |
| Arm/Group Title | Tablets | Gelcaps |
|---|---|---|
| Arm/Group Description | Patients in this arm will receive levothyroxine tablets (encapsulated for blinding purposes) Levothyroxine: Patients post-thyroidectomy will receive either levothyroxine in tablet form or in gelcaps | Patients in this arm will receive levothyroxine gelcaps (encapsulated for blinding purposes) Levothyroxine: Patients post-thyroidectomy will receive either levothyroxine in tablet form or in gelcaps |
| Measure Participants | 5 | 5 |
| Mean (Standard Deviation) [score on a scale] |
39.2
(3.70)
|
39
(3)
|
Adverse Events
| Time Frame | 18 weeks (until completion of the study) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | All 14 subjects were considered at risk for adverse events | |||
| Arm/Group Title | Tablets | Gelcaps | ||
| Arm/Group Description | Patients in this arm will receive levothyroxine tablets (encapsulated for blinding purposes) Levothyroxine: Patients post-thyroidectomy will receive either levothyroxine in tablet form or in gelcaps | Patients in this arm will receive levothyroxine gelcaps (encapsulated for blinding purposes) Levothyroxine: Patients post-thyroidectomy will receive either levothyroxine in tablet form or in gelcaps | ||
All Cause Mortality |
||||
| Tablets | Gelcaps | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/8 (0%) | ||
Serious Adverse Events |
||||
| Tablets | Gelcaps | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/8 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Tablets | Gelcaps | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/6 (66.7%) | 3/8 (37.5%) | ||
| Endocrine disorders | ||||
| fatigue | 1/6 (16.7%) | 1 | 1/8 (12.5%) | 1 |
| hypocalcemia | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 |
| Gastrointestinal disorders | ||||
| GERD | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 |
| abdominal pain | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| back pain | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 |
| Nervous system disorders | ||||
| anxiety | 1/6 (16.7%) | 1 | 1/8 (12.5%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| psoriasis | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 |
| rosacea | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Dr. Alex Tessnow-ASSOC PROFESSOR |
|---|---|
| Organization | UT Southwestern Medical Center |
| Phone | 214/648-3685 |
| Alex.Tessnow@UTSouthwestern.edu |
- STU 022015-044