Clinical Trial: Mechanistic Study of Subclinical Hypothyroidism In the Elderly

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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.

Detailed Summary:
Sponsor: University of Pennsylvania

Current Primary Outcome:

• TSH area under the curve [ Time Frame: Up to 25 weeks on each drug ]
  Difference between baseline assessment and assessment when TSH is at goal (up to 25 weeks) will be performed separately for each drug (LT4 and LT3)
• TSH Max [ Time Frame: Up to 25 weeks on each drug, when TSH is at goal ]
  Difference between baseline assessment and assessment when TSH is at goal (up to 25 weeks) will be performed separately for each drug (LT4 and LT3)
• Free T4 Level [ Time Frame: Up to 25 weeks on each drug, when TSH is at goal ]
  Difference between baseline assessment and assessment when TSH is at goal (up to 25 weeks) will be performed separately for each drug (LT4 and LT3)
• Total T3 Level [ Time Frame: Up to 25 weeks on each drug, when TSH is at goal ]
  Difference between baseline assessment and assessment when TSH is at goal (up to 25 weeks) will be performed separately for each drug (LT4 and LT3)
• TSH bioactivity measurement [ Time Frame: Up to 25 weeks on each drug, when TSH is at goal ]
  Measurement of cAMP content via immunoassay following human-embryonic kidney-TSH receptor cell incubation with TSH molecule ligand.

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Unstimulated TSH bioactivity [ Time Frame: Up to 25 weeks on each drug, 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: Up to 25 weeks on each drug, when TSH is at goal ]
  REE evaluation by indirect calorimetry
• Weight [ Time Frame: Up to 25 weeks on each drug, when TSH is at goal ]
• Body Fat Percent [ Time Frame: Up to 25 weeks on each drug, when TSH is at goal ]
  Measured by dual energy x-ray absorptiometry (DXA)
• Body Fat Total [ Time Frame: Up to 25 weeks on each drug, when TSH is at goal ]
  Measured by dual energy x-ray absorptiometry (DXA)
• Free Fat Mass [ Time Frame: Up to 25 weeks on each drug, when TSH is at goal ]
  Measured by dual energy x-ray absorptiometry (DXA)
• Bone Density [ Time Frame: Up to 25 weeks on each drug, when TSH is at goal ]
  Measured by dual energy x-ray absorptiometry (DXA)
• Lipid Profile [ Time Frame: Up to 25 weeks on each drug, when TSH is at goal ]
• SF-36 [ Time Frame: Up to 25 weeks on each drug, when TSH is at goal ]
  Quality of Life Questionnaire
• Heart Rate [ Time Frame: Up to 25 weeks on each drug, when TSH is at goal ]
  measured by actigraphy monitor
• Physical Activity [ Time Frame: Up to 25 weeks on each drug, when TSH is at goal ]
  measured by actigraphy monitor
• Digit Symbol Substitution Test [ Time Frame: Up to 25 weeks on each drug, when TSH is at goal ]
• Body Temperature [ Time Frame: Up to 25 weeks on each drug, when TSH is at goal ]
  Rectal Temperature
• Hypothyroid Symptom Questionnaire [ Time Frame: Up to 25 weeks on each drug, when TSH is at goal ]

Original Secondary Outcome: Same as current

Information By: University of Pennsylvania

Dates:
Date Received: February 3, 2015
Date Started: January 2015
Date Completion: April 2018
Last Updated: April 11, 2016
Last Verified: April 2016