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

NCT02317926 | Unknown

• 1 other identifier: 397401-1
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Hypothyroidism

Outcome Measures

Primary Outcomes (4)

• Wechsler memory scale, fourth edition (WMS-IV)

  Pearson, PsychCorp, San Antonio, Texas

  3 months

• Beck Depression Inventory

  Pearson, PsychCorp

  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.

  3 months

• QOL as measured by General Health Questionnaire (GHQ)-12

  3 months

Study Arms (3)

Levothyroxine Plus Liothyronine Group

ACTIVE COMPARATOR

Levothyroxine Plus Liothyronine Group

Drug: Levothyroxine Plus Liothyronine

Levothyroxine Group

ACTIVE COMPARATOR

Levothyroxine Group

Drug: Levothyroxine

Desiccated Thyroid Extract Group

ACTIVE COMPARATOR

Desiccated Thyroid Extract Group

Drug: Desiccated Thyroid Extract

Interventions

Levothyroxine DRUG

Levothyroxine Group

Levothyroxine Plus Liothyronine DRUG

Levothyroxine Plus Liothyronine Group

Desiccated Thyroid Extract DRUG

Desiccated Thyroid Extract Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Walter Reed National Military Medical Center: lead

Study Sites (1)

Walter Reed National Military Medical Center

Besthesda, Maryland, 20889, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 34185829 DERIVED

MeSH Terms

Conditions

Hypothyroidism

Interventions

Thyroxine; Triiodothyronine; Thyroid (USP)

Condition Hierarchy (Ancestors)

Thyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Thyronines

Central Study Contacts

Mohamed K Shakir, MD

CONTACT

301-295-5165; mohamed.k.shakir.civ@mail.mil

Angela Taylor

CONTACT

301-295-5165; angela.l.taylor38.civ@mail.mil

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Endocrinologist

Study Record Dates

• First Submitted: December 8, 2014
• First Posted: December 17, 2014
• Study Start: May 1, 2015
• Primary Completion: May 1, 2018
• Last Updated: May 6, 2015

Record last verified: 2015-05

Locations

US (1)