HypothyroidismNCT02317926
Desiccated Thyroid Extract Versus Synthetic T3/T4 Combination (ThyrolarTM) Versus L-T4 Alone in the Therapy of Primary Hypothyroidism With Special Attention to the Gene Polymorphism
A study testing Levothyroxine, Levothyroxine Plus Liothyronine and Desiccated Thyroid Extract in people with Hypothyroidism, run by Walter Reed National Military Medical Center at 1 site in United States.
Trial summary
The proposed study design is a prospective, randomized, double-blind, crossover study. After informed consent is obtained, patients will be randomized to receive either desiccated thyroid in capsules, or L-T4/L-T3 (ThyrolarTM) in capsules, or L-T4 alone capsules. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypothyroidism
- What is being tested?
- Levothyroxine, Levothyroxine Plus Liothyronine and Desiccated Thyroid Extract
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 1 siteUnited States
- Study dates
- May 2015to May 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects will be between the ages of 18 to 65 and will have been on levothyroxine for primary hypothyroidism for at least 6 months
- Department of Defense beneficiaries living within 60 miles of Besthesda, MD
Who cannot join
- Subjects will be excluded if they have the following problems: pregnancy, plan for pregnancy in the next 12 months, cardiac disease, especially coronary artery disease, chronic obstructive lung disease, malabsorption disorder, gastrointestinal surgeries, significant renal or liver dysfunction, seizure disorders, thyroid and non-thyroid active cancers, uncontrolled psychosis, psychotropic medication use, steroid use, amiodarone, chemotherapy for cancer, iron supplement more than 325mg per day, carafate/ proton pump inhibitor use, cholestyramine use, and those with recent orders who are expected to move out of the geographic area, age less than 18 years old or older than 65 years old. Patients scheduled for deployment will be excluded.
- Subjects with subclinical hypothyroidism will be excluded. If we include patients with subclinical hypothyroidism, it will be difficult to assess the outcomes. This is because only a very small percentage of patients with subclinical hypothyroidism benefit from thyroid hormone therapy and therefore, a cross-over study as done in this project will not show a difference between the therapies.
- Females of child-bearing age will be screened with initial assessment for pregnancy as part of standard of care (eg history of amnenorrhea and/or positive pregnancy testing via hCG). There is no experience in using desiccated thyroid extract in pregnant women and there is no published paper in this area. Desiccated thyroid extract is rated Category-A drug in pregnancy which means there are no known risks to the fetus.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Walter Reed National Military Medical Center
Besthesda, Maryland, 20889
Mohamed K Shakir, MD, 301-295-5165, mohamed.k.shakir.civ@mail.mil
Angela Taylor, 301-295-5165, angela.l.taylor38.civ@mail.mil@mail.mil
About this study
The proposed study design is a prospective, randomized, double-blind, crossover study. After informed consent is obtained, patients will be randomized to receive either desiccated thyroid in capsules, or L-T4/L-T3 (ThyrolarTM) in capsules, or L-T4 alone capsules. All study participants, physician investigators, those administering the neurocognitive tests and those analyzing test results will be blinded throughout the study.
Subjects will undergo memory testing, a disease specific symptom questionnaire, a general mental health assessment, a complete physical examination, baseline EKG, and biochemical testing consisting of serum TSH, free T4, total T4, total T3, free T3, T3 resin uptake, reverse T3, sex hormone binding globulin (SHBG), serum iodine, a lipid panel, insulin, glucose and leptin. This testing and DXA scan of body composition will be performed at baseline and after each 3 month treatment period. Deiodinase type 2 (DIO2) polymorphisms analyses - will also be performed at the beginning of the study and the results will be blinded to the investigators performing the memory testing.
Read more
After 5-6 weeks on the study medication, TSH levels will be checked and the medication adjusted to maintain TSH level between 0.46-4.68 mIU/L. Once the TSH level is in the desired range, subjects will continue the medication for an additional 6 weeks. Subjects will then be crossed-over to the other treatment arm for 3 months. Again, testing will be performed after each treatment period. Finally the subjects will again switched over to the 3rd arm and testing will be performed after treatment period.
A cross-over design is preferred because we are assessing subjective symptoms such as clinical well-being and other parameters. Therefore, we will be able to evaluate the effectiveness of L-T4/T3 (ThyrolarTM) vs DTE vs T4 alone in the same patientssubjects. This is also supported by the previous study by Escobar-Morreale et al.
Additionally, the Wechsler memory scale, DEXA for body composition, measurment of reverse T3, insulin, leptin, and DIO2 polymorphisms analysis will be included for the research portion of this study. Further, the frequency of serum blood draws, for research purposes, will be at intervals of 0, 6, 12, 18, 24, 30 and 36 weeks.
- Conditions
- Hypothyroidism
- Being tested
- Levothyroxine, Levothyroxine Plus Liothyronine, Desiccated Thyroid Extract
- Medical subject headings
- Hypothyroidism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevothyroxineDrug
Levothyroxine Plus LiothyronineDrug
Desiccated Thyroid ExtractDrug
| Study group | Role | What they receive |
|---|---|---|
| Levothyroxine Plus Liothyronine Group | Active comparator | Levothyroxine Plus Liothyronine Group Receives: Drug: Levothyroxine Plus Liothyronine |
| Levothyroxine Group | Active comparator | Levothyroxine Group Receives: Drug: Levothyroxine |
| Desiccated Thyroid Extract Group | Active comparator | Desiccated Thyroid Extract Group Receives: Drug: Desiccated Thyroid Extract |
What is being measured
The primary outcome is the main question the study is designed to answer.
Wechsler memory scale, fourth edition (WMS-IV)
Pearson, PsychCorp, San Antonio, Texas
Measured: 3 months
Beck Depression Inventory
Pearson, PsychCorp
Measured: 3 months
Thyroid Symptom Questionnaire (TSQ)
Clyde PW, Harari AE, Getka EJ, Shakir KM. Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial. JAMA. 2003; 290:2952-2958.
Measured: 3 months
QOL as measured by General Health Questionnaire (GHQ)-12
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2014 (estimated)
- Study startMay 2015
- Primary completionMay 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypothyroidismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 81 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Walter Reed National Military Medical Center
- Sponsor type
- US federal agency
- Responsible party
- Principal investigator, Mohamed K.M. Shakir, Walter Reed National Military Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02317926
- Sponsor's protocol ID
- 397401-1
- Status last verified
- May 2015
- First submitted
- 8 Dec 2014
- Last updated
- 6 May 2015
- Results posted
- No
Publications
Shakir MKM, Brooks DI, McAninch EA, Fonseca TL, Mai VQ, Bianco AC, Hoang TD. Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism. J Clin Endocrinol Metab. 2021 Oct 21;106(11):e4400-e4413. doi: 10.1210/clinem/dgab478.
PubMed 34185829
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Desiccated Thyroid Extract Versus Synthetic T3/T4 Combination (ThyrolarTM) Versus L-T4 Alone in the Therapy of Primary Hypothyroidism With Special Attention to the Gene Polymorphism
- ClinicalTrials.gov ID
- NCT02317926
- Acronym / sponsor ID
- 397401-1
- Conditions
- Hypothyroidism
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 81 participants (estimated)
- Lead sponsor
- Walter Reed National Military Medical CenterUS federal agency
- Study start
- May 2015
- Primary completion
- May 2018 (estimated)
- First posted
- 17 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed study design is a prospective, randomized, double-blind, crossover study. After informed consent is obtained, patients will be randomized to receive either desiccated thyroid in capsules, or L-T4/L-T3 (ThyrolarTM) in capsules, or L-T4 alone capsules. All study participants, physician investigators, those administering the neurocognitive tests and those analyzing test results will be blinded throughout the study.
Subjects will undergo memory testing, a disease specific symptom questionnaire, a general mental health assessment, a complete physical examination, baseline EKG, and biochemical testing consisting of serum TSH, free T4, total T4, total T3, free T3, T3 resin uptake, reverse T3, sex hormone binding globulin (SHBG), serum iodine, a lipid panel, insulin, glucose and leptin. This testing and DXA scan of body composition will be performed at baseline and after each 3 month treatment period. Deiodinase type 2 (DIO2) polymorphisms analyses - will also be performed at the beginning of the study and the results will be blinded to the investigators performing the memory testing.
After 5-6 weeks on the study medication, TSH levels will be checked and the medication adjusted to maintain TSH level between 0.46-4.68 mIU/L. Once the TSH level is in the desired range, subjects will continue the medication for an additional 6 weeks. Subjects will then be crossed-over to the other treatment arm for 3 months. Again, testing will be performed after each treatment period. Finally the subjects will again switched over to the 3rd arm and testing will be performed after treatment period.
A cross-over design is preferred because we are assessing subjective symptoms such as clinical well-being and other parameters. Therefore, we will be able to evaluate the effectiveness of L-T4/T3 (ThyrolarTM) vs DTE vs T4 alone in the same patientssubjects. This is also supported by the previous study by Escobar-Morreale et al.
Additionally, the Wechsler memory scale, DEXA for body composition, measurment of reverse T3, insulin, leptin, and DIO2 polymorphisms analysis will be included for the research portion of this study. Further, the frequency of serum blood draws, for research purposes, will be at intervals of 0, 6, 12, 18, 24, 30 and 36 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Levothyroxine Plus Liothyronine Group | Active comparator | Drug: Levothyroxine Plus LiothyronineLevothyroxine Plus Liothyronine Group |
| Levothyroxine Group | Active comparator | Drug: LevothyroxineLevothyroxine Group |
| Desiccated Thyroid Extract Group | Active comparator | Drug: Desiccated Thyroid ExtractDesiccated Thyroid Extract Group |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Subjects will be between the ages of 18 to 65 and will have been on levothyroxine for primary hypothyroidism for at least 6 months
- Department of Defense beneficiaries living within 60 miles of Besthesda, MD
Key exclusion criteria (3 listed)
- Subjects will be excluded if they have the following problems: pregnancy, plan for pregnancy in the next 12 months, cardiac disease, especially coronary artery disease, chronic obstructive lung disease, malabsorption disorder, gastrointestinal surgeries, significant renal or liver dysfunction, seizure disorders, thyroid and non-thyroid active cancers, uncontrolled psychosis, psychotropic medication use, steroid use, amiodarone, chemotherapy for cancer, iron supplement more than 325mg per day, carafate/ proton pump inhibitor use, cholestyramine use, and those with recent orders who are expected to move out of the geographic area, age less than 18 years old or older than 65 years old. Patients scheduled for deployment will be excluded.
- Subjects with subclinical hypothyroidism will be excluded. If we include patients with subclinical hypothyroidism, it will be difficult to assess the outcomes. This is because only a very small percentage of patients with subclinical hypothyroidism benefit from thyroid hormone therapy and therefore, a cross-over study as done in this project will not show a difference between the therapies.
- Females of child-bearing age will be screened with initial assessment for pregnancy as part of standard of care (eg history of amnenorrhea and/or positive pregnancy testing via hCG). There is no experience in using desiccated thyroid extract in pregnant women and there is no published paper in this area. Desiccated thyroid extract is rated Category-A drug in pregnancy which means there are no known risks to the fetus.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Levothyroxine | Drug | Levothyroxine Group |
| Levothyroxine Plus Liothyronine | Drug | Levothyroxine Plus Liothyronine Group |
| Desiccated Thyroid Extract | Drug | Desiccated Thyroid Extract Group |
Primary outcome
Wechsler memory scale, fourth edition (WMS-IV)
Time frame: 3 months
Pearson, PsychCorp, San Antonio, Texas
Beck Depression Inventory
Time frame: 3 months
Pearson, PsychCorp
Thyroid Symptom Questionnaire (TSQ)
Time frame: 3 months
Clyde PW, Harari AE, Getka EJ, Shakir KM. Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial. JAMA. 2003; 290:2952-2958.
QOL as measured by General Health Questionnaire (GHQ)-12
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2015.
- Derived from this study: PubMed 34185829Shakir MKM, Brooks DI, McAninch EA, Fonseca TL, Mai VQ, Bianco AC, Hoang TD. Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism. J Clin Endocrinol Metab. 2021 Oct 21;106(11):e4400-e4413. doi: 10.1210/clinem/dgab478.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Levothyroxine, Levothyroxine Plus Liothyronine and Desiccated Thyroid Extract in people with Hypothyroidism, run by Walter Reed National Military Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mohamed K Shakir, MD (301-295-5165, mohamed.k.shakir.civ@mail.mil), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Wechsler memory scale, fourth edition (WMS-IV) (time frame: 3 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02317926, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2015.