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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

This study is currently recruiting participants.
Verified May 2015 by Mohamed K.M. Shakir, Walter Reed National Military Medical Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT02317926
First Posted: December 17, 2014
Last Update Posted: May 6, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Mohamed K.M. Shakir, Walter Reed National Military Medical Center
  Purpose

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.


Condition Intervention
Hypothyroidism Drug: Levothyroxine Drug: Levothyroxine Plus Liothyronine Drug: Desiccated Thyroid Extract

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Mohamed K.M. Shakir, Walter Reed National Military Medical Center:

Primary Outcome Measures:
  • 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 ]

Estimated Enrollment: 81
Study Start Date: May 2015
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Levothyroxine Plus Liothyronine Group
Levothyroxine Plus Liothyronine Group
Drug: Levothyroxine Plus Liothyronine
Active Comparator: Levothyroxine Group
Levothyroxine Group
Drug: Levothyroxine
Active Comparator: Desiccated Thyroid Extract Group
Desiccated Thyroid Extract Group
Drug: Desiccated Thyroid Extract

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02317926


Contacts
Contact: Mohamed K Shakir, MD 301-295-5165 mohamed.k.shakir.civ@mail.mil
Contact: Angela Taylor 301-295-5165 angela.l.taylor38.civ@mail.mil

Locations
United States, Maryland
Walter Reed National Military Medical Center Recruiting
Besthesda, Maryland, United States, 20889
Contact: Mohamed K Shakir, MD    301-295-5165    mohamed.k.shakir.civ@mail.mil   
Contact: Angela Taylor    301-295-5165    angela.l.taylor38.civ@mail.mil@mail.mil   
Sponsors and Collaborators
Walter Reed National Military Medical Center
  More Information

Responsible Party: Mohamed K.M. Shakir, Staff Endocrinologist, Walter Reed National Military Medical Center
ClinicalTrials.gov Identifier: NCT02317926     History of Changes
Other Study ID Numbers: 397401-1
First Submitted: December 8, 2014
First Posted: December 17, 2014
Last Update Posted: May 6, 2015
Last Verified: May 2015

Additional relevant MeSH terms:
Hypothyroidism
Thyroid Diseases
Endocrine System Diseases