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Mechanistic Study of Subclinical Hypothyroidism In the Elderly

Primary Purpose

Subclinical Hypothyroidism

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Levothyroxine
Liothyronine
Thyrotropin-Releasing Hormone
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Subclinical Hypothyroidism focused on measuring Levothyroxine, Liothyronine, Thyrotropin Releasing Hormone, Aging, Hypothyroidism, Thyroid diseases

Eligibility Criteria

70 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Levothyroxine First

Liothyronine First

Arm Description

Participants will start on the thyroid hormone Levothyroxine prior to crossing over to Liothyronine

Participants will start on the thyroid hormone Liothyronine prior to crossing over to Levothyroxine

Outcomes

Primary Outcome Measures

TSH Area Under the Curve
TSH area under the curve within 60 minutes of TRH stimulation when TSH is at goal
TSH Max
The maximum concentration of TSH after TRH stimulation when TSH is at goal
Free T4 Level
Free thyroxine level when TSH level is at goal on therapy.
Total T3 Level
Total triiodothyronine level when TSH is at goal on therapy

Secondary Outcome Measures

Full Information

First Posted
February 3, 2015
Last Updated
February 16, 2021
Sponsor
University of Pennsylvania
Collaborators
National Institute on Aging (NIA)
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1. Study Identification

Unique Protocol Identification Number
NCT02399475
Brief Title
Mechanistic Study of Subclinical Hypothyroidism In the Elderly
Official Title
The Thyroid Axis in Older Individuals With Persistent Subclinical Hypothyroidism: a Mechanistic, Randomized, Double-Blind, Cross-Over Study of Levothyroxine and Liothyronine Administration
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
January 1, 2015 (Actual)
Primary Completion Date
September 30, 2019 (Actual)
Study Completion Date
September 30, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania
Collaborators
National Institute on Aging (NIA)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Subclinical Hypothyroidism
Keywords
Levothyroxine, Liothyronine, Thyrotropin Releasing Hormone, Aging, Hypothyroidism, Thyroid diseases

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Levothyroxine First
Arm Type
Experimental
Arm Description
Participants will start on the thyroid hormone Levothyroxine prior to crossing over to Liothyronine
Arm Title
Liothyronine First
Arm Type
Experimental
Arm Description
Participants will start on the thyroid hormone Liothyronine prior to crossing over to Levothyroxine
Intervention Type
Drug
Intervention Name(s)
Levothyroxine
Other Intervention Name(s)
Synthroid
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Liothyronine
Other Intervention Name(s)
Cytomel
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Thyrotropin-Releasing Hormone
Intervention Description
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).
Primary Outcome Measure Information:
Title
TSH Area Under the Curve
Description
TSH area under the curve within 60 minutes of TRH stimulation when TSH is at goal
Time Frame
0, 5, 10, 15, 20, 30, and 60 min post TRH
Title
TSH Max
Description
The maximum concentration of TSH after TRH stimulation when TSH is at goal
Time Frame
Between 0 and 180 min after TRH stimulation
Title
Free T4 Level
Description
Free thyroxine level when TSH level is at goal on therapy.
Time Frame
An average of 7 months after initiating therapy
Title
Total T3 Level
Description
Total triiodothyronine level when TSH is at goal on therapy
Time Frame
An average of 7 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: men and women aged 70 and older TSH between 4.5 and 19.9 mU/L as an outpatient ability to provide informed consent Exclusion Criteria: Laboratory Tests: 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 thyroid peroxidase (TPO) antibody positive abnormal liver function tests (LFTs >3 x upper limit of normal) hemoglobin <11 g/dL Surgeries or Procedures: thyroid surgery pituitary surgery bariatric surgery bowel resection involving the jejunum and upper ileum radioactive iodine therapy radiation treatments to head or neck Medical Conditions: diagnosis of pituitary disease diagnosis of amyloidosis, sarcoidosis, hemochromatosis diagnosis of adrenal insufficiency obesity with BMI > 35 mg/kg2 history of stroke chronic or ongoing angina, Class II or higher congestive heart failure, or uncontrolled hypertension with current blood pressure greater than 160/100 diabetes mellitus with hemoglobin A1C level greater than 8.0% in the past six months celiac sprue, Crohn's disease, ulcerative colitis, Zollinger-Ellison syndrome renal insufficiency with calculated glomerular filtration rate <45 cc/min cognitive impairment with Mini Mental State Exam[30] <24/30 history of any seizures unstable medical or psychological condition in the judgment of the principal investigator Medications: thyroid hormone preparations antithyroid drugs medications that interfere with the absorption or metabolism of thyroid hormone medications that interfere with the TRH stimulation test proton pump inhibitors
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne R Cappola, MD, ScM
Organizational Affiliation
The University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

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Mechanistic Study of Subclinical Hypothyroidism In the Elderly

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