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Mechanistic Study of Subclinical Hypothyroidism In the Elderly

This study is currently recruiting participants.
Verified June 2017 by University of Pennsylvania
Sponsor:
ClinicalTrials.gov Identifier:
NCT02399475
First Posted: March 26, 2015
Last Update Posted: June 22, 2017
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.
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
University of Pennsylvania
  Purpose
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.

Condition Intervention
Subclinical Hypothyroidism Drug: Levothyroxine Drug: Liothyronine Drug: Thyrotropin-Releasing Hormone

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
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

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • TSH area under the curve [ Time Frame: When TSH is at goal ]
    Difference between baseline assessment and assessment when TSH is at goal will be performed separately for each drug (LT4 and LT3)

  • TSH Max [ Time Frame: When TSH is at goal ]
    Difference between baseline assessment and assessment when TSH is at goal will be performed separately for each drug (LT4 and LT3)

  • Free T4 Level [ Time Frame: When TSH is at goal ]
    Difference between baseline assessment and assessment when TSH is at goal will be performed separately for each drug (LT4 and LT3)

  • Total T3 Level [ Time Frame: When TSH is at goal ]
    Difference between baseline assessment and assessment when TSH is at goal will be performed separately for each drug (LT4 and LT3)

  • TSH bioactivity measurement [ Time Frame: When TSH is at goal ]
    Measurement of cAMP content via immunoassay following human-embryonic kidney-TSH receptor cell incubation with TSH molecule ligand.


Secondary Outcome Measures:
  • Unstimulated TSH bioactivity [ Time Frame: When TSH is at goal ]
    Measurement of cAMP content via immunoassay following human-embryonic kidney-TSH receptor cell incubation with TSH molecule ligand.

  • Resting energy expenditure (REE) evaluation [ Time Frame: When TSH is at goal ]
    REE evaluation by indirect calorimetry

  • Weight [ Time Frame: When TSH is at goal ]
  • Body Fat Percent [ Time Frame: When TSH is at goal ]
    Measured by dual energy x-ray absorptiometry (DXA)

  • Body Fat Total [ Time Frame: When TSH is at goal ]
    Measured by dual energy x-ray absorptiometry (DXA)

  • Free Fat Mass [ Time Frame: When TSH is at goal ]
    Measured by dual energy x-ray absorptiometry (DXA)

  • Bone Density [ Time Frame: When TSH is at goal ]
    Measured by dual energy x-ray absorptiometry (DXA)

  • Lipid Profile [ Time Frame: When TSH is at goal ]
  • SF-36 [ Time Frame: When TSH is at goal ]
    Quality of Life Questionnaire

  • Heart Rate [ Time Frame: When TSH is at goal ]
    measured by actigraphy monitor

  • Physical Activity [ Time Frame: When TSH is at goal ]
    measured by actigraphy monitor

  • Digit Symbol Substitution Test [ Time Frame: When TSH is at goal ]
  • Body Temperature [ Time Frame: When TSH is at goal ]
    Rectal Temperature

  • Hypothyroid Symptom Questionnaire [ Time Frame: When TSH is at goal ]

Estimated Enrollment: 30
Study Start Date: January 2015
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: 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).

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   70 Years and older   (Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. history of myocardial infarction, coronary artery bypass graft surgery or percutaneous coronary angioplasty, angina, atrial fibrillation, 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
  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): NCT02399475


Contacts
Contact: Theresa Scattergood, RN, MSN 215-898-5664 Terry.Scattergood@uphs.upenn.edu

Locations
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
National Institute on Aging (NIA)
Investigators
Principal Investigator: Anne R Cappola, MD, ScM The University of Pennsylvania
  More Information

Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02399475     History of Changes
Other Study ID Numbers: 821564
K24AG042765-01A1 ( U.S. NIH Grant/Contract )
First Submitted: February 3, 2015
First Posted: March 26, 2015
Last Update Posted: June 22, 2017
Last Verified: June 2017

Keywords provided by University of Pennsylvania:
Levothyroxine
Liothyronine
Thyrotropin Releasing Hormone
Aging
Hypothyroidism
Thyroid diseases

Additional relevant MeSH terms:
Hypothyroidism
Thyroid Diseases
Endocrine System Diseases
Hormones
Thyrotropin-Releasing Hormone
Calcitonin
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Bone Density Conservation Agents