Mechanistic Study of Subclinical Hypothyroidism In the Elderly

February 16, 2021 updated by: University of Pennsylvania

The Thyroid Axis in Older Individuals With Persistent Subclinical Hypothyroidism: a Mechanistic, Randomized, Double-Blind, Cross-Over Study of Levothyroxine and Liothyronine Administration

Subclinical hypothyroidism, defined as an elevated TSH in the setting of normal thyroid hormone levels, is a common diagnosis in the elderly. The purpose of this study is to examine the hypothalamic-pituitary-thyroid axis in men and women aged 70 years and older with persistent subclinical hypothyroidism. To evaluate the mechanism behind this condition, participants will undergo thyrotropin releasing hormone stimulation testing at 3 visits: baseline and while taking two different thyroid hormone preparations, levothyroxine and liothyronine. The investigators will also assess physiologic responses to these two different thyroid hormone medications to help us understand how the thyroid works in advanced age.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

68 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. men and women aged 70 and older
  2. TSH between 4.5 and 19.9 mU/L as an outpatient
  3. ability to provide informed consent

Exclusion Criteria:

Laboratory Tests:

  1. TSH <4.5 mU/L or >20 mU/L on repeat testing at least four weeks later or free T4 level outside the reference range
  2. thyroid peroxidase (TPO) antibody positive
  3. abnormal liver function tests (LFTs >3 x upper limit of normal)
  4. hemoglobin <11 g/dL

Surgeries or Procedures:

  1. thyroid surgery
  2. pituitary surgery
  3. bariatric surgery
  4. bowel resection involving the jejunum and upper ileum
  5. radioactive iodine therapy
  6. radiation treatments to head or neck

Medical Conditions:

  1. diagnosis of pituitary disease
  2. diagnosis of amyloidosis, sarcoidosis, hemochromatosis
  3. diagnosis of adrenal insufficiency
  4. obesity with BMI > 35 mg/kg2
  5. history of stroke
  6. chronic or ongoing angina, Class II or higher congestive heart failure, or uncontrolled hypertension with current blood pressure greater than 160/100
  7. diabetes mellitus with hemoglobin A1C level greater than 8.0% in the past six months
  8. celiac sprue, Crohn's disease, ulcerative colitis, Zollinger-Ellison syndrome
  9. renal insufficiency with calculated glomerular filtration rate <45 cc/min
  10. cognitive impairment with Mini Mental State Exam[30] <24/30
  11. history of any seizures
  12. unstable medical or psychological condition in the judgment of the principal investigator

Medications:

  1. thyroid hormone preparations
  2. antithyroid drugs
  3. medications that interfere with the absorption or metabolism of thyroid hormone
  4. medications that interfere with the TRH stimulation test
  5. proton pump inhibitors

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Levothyroxine First
Participants will start on the thyroid hormone Levothyroxine prior to crossing over to Liothyronine
Drug: Levothyroxine
Oral levothyroxine with a total starting dose of 0.7mcg/kg/day split into three daily doses will be titrated to a target TSH level of 0.5 -1.5mU/L
Other Names:
  • Synthroid
Drug: Liothyronine
Oral liothyronine with a starting dose of 1/3 of the weight-based LT4 dose divided into three daily doses titrated to a target TSH level of 0.5 -1.5mU/L
Other Names:
  • Cytomel
Drug: Thyrotropin-Releasing Hormone
200 µg intravenous TRH will be given at study visit 1 (baseline), study visit 2 (on first thyroid treatment), and study visit 3 (on second thyroid treatment).
Experimental: Liothyronine First
Participants will start on the thyroid hormone Liothyronine prior to crossing over to Levothyroxine
Drug: Levothyroxine
Oral levothyroxine with a total starting dose of 0.7mcg/kg/day split into three daily doses will be titrated to a target TSH level of 0.5 -1.5mU/L
Other Names:
  • Synthroid
Drug: Liothyronine
Oral liothyronine with a starting dose of 1/3 of the weight-based LT4 dose divided into three daily doses titrated to a target TSH level of 0.5 -1.5mU/L
Other Names:
  • Cytomel
Drug: Thyrotropin-Releasing Hormone
200 µg intravenous TRH will be given at study visit 1 (baseline), study visit 2 (on first thyroid treatment), and study visit 3 (on second thyroid treatment).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
TSH Area Under the Curve
Time Frame: 0, 5, 10, 15, 20, 30, and 60 min post TRH
TSH area under the curve within 60 minutes of TRH stimulation when TSH is at goal
0, 5, 10, 15, 20, 30, and 60 min post TRH
TSH Max
Time Frame: Between 0 and 180 min after TRH stimulation
The maximum concentration of TSH after TRH stimulation when TSH is at goal
Between 0 and 180 min after TRH stimulation
Free T4 Level
Time Frame: An average of 7 months after initiating therapy
Free thyroxine level when TSH level is at goal on therapy.
An average of 7 months after initiating therapy
Total T3 Level
Time Frame: An average of 7 months
Total triiodothyronine level when TSH is at goal on therapy
An average of 7 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Collaborators

National Institute on Aging (NIA)

Investigators

  • Principal Investigator: Anne R Cappola, MD, ScM, The University of Pennsylvania

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2015

Primary Completion (Actual)

September 30, 2019

Study Completion (Actual)

September 30, 2019

Study Registration Dates

First Submitted

February 3, 2015

First Submitted That Met QC Criteria

March 20, 2015

First Posted (Estimate)

March 26, 2015

Study Record Updates

Last Update Posted (Actual)

March 9, 2021

Last Update Submitted That Met QC Criteria

February 16, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 821564
  • K24AG042765-01A1 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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