Neurocognitive and Metabolic Effects of Mild Hypothyroidism

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mary Samuels, Oregon Health and Science University
ClinicalTrials.gov Identifier:
NCT00565864
First received: November 28, 2007
Last updated: November 7, 2013
Last verified: November 2013

November 28, 2007
November 7, 2013
August 2008
August 2013   (final data collection date for primary outcome measure)
Cognitive measures, quality of life, mood assessed by the SCL-90R, SF-36, and/or POMS subscales. Metabolic outcomes assessed by DEXA, indirect calorimetry & doubly labeled water [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Cognitive measures, quality of life, mood assessed by the SCL-90R, SF-36, and/or POMS subscales. Metabolic outcomes assessed by DEXA, indirect calorimetry [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00565864 on ClinicalTrials.gov Archive Site
To assess whether changes in cognition or mood depend upon REE and other body composition measures. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
To assess whether changes in cognition or mood depend upon REE and other body compositon measures. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Neurocognitive and Metabolic Effects of Mild Hypothyroidism
Neurocognitive and Metabolic Effects of Mild Hypothyroidism

Patients with hypothyroidism are routinely treated with thyroid hormone (l-thyroxine) for replacement therapy. Physicians monitor the thyroid hormone dose by measuring a thyroid stimulating hormone (TSH) level in the blood, with the goal of a normal level. However, recent data suggest that the "normal" TSH range is too broad, and that patients may still have symptoms if their TSH levels are at the top or bottom part of the normal range.

To study this issue, it is useful to address issues such as general health status, psychological symptoms, mood, memory, and metabolic status, since thyroid hormone has major effects on the brain adn metabolism, and since patients with treated hypothyroidism often have symptoms related to these areas.

In the present study, otherwise healthy subjects with treated hypothyroidism, ages 20-75 years, will be enrolled in a 7-11month study. At baseline, they will have tests of health status, psychological symptoms, mood, memory, body composition, and energy expenditure performed. Following these baseline measurements, subjects will receive either their usual doses of l-thyroxine, or a slightly higher or lower dose. The doses will be chosen to try to achieve either a low-normal TSH level, a high-normal TSH level, or a mildly elevated TSH level. Which target TSH the patient is assigned will be determined randomly, and neither the subject nor the study contacts will know which dose the patient is receiving. Subjects will be seen every 6 weeks during the study for brief visits to make sure they are not having any side effects, and to adjust the l-thyroxine doses if the TSH has not yet reached the target range. At the 24-week visit (end of study), the subjects will undergo the same tests that they had on the baseline visit.

Results from the study will be examined to see if minor changes in TSH or other thyroid hormone levels cause changes in any of the outcomes, and if the degree of TSH change correlates with the degree of outcome changes. These results may help physicians caring for patients with thyroid disease better determine the optimal dose of thyroid hormone for each patient.

Not Provided
Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Hypothyroidism
Drug: L-thyroxine (L-T4)
L-thyroxine at doses appropriate to attain target TSH levels for the different arms for 24 weeks
Other Names:
  • Subjects will remain on their usual brand of L-T4.
  • Subjects on generic L-T4 will be switched to Levoxyl.
  • Experimental: 1-A
    Subjects with baseline TSH between 0.28 and 2.49. Treatment arm 1-A targets a THS of 0.28 -2.49 mU/L (the theoretical optimal range).
    Intervention: Drug: L-thyroxine (L-T4)
  • Experimental: 1-B
    Subjects with baseline TSH levels between 0.28 and 2.49 mU/L, Treatment arm 1-B targeting a TSH of 2.5 - 5.0 mU/L
    Intervention: Drug: L-thyroxine (L-T4)
  • Experimental: 1-C
    Subjects with baseline TSH levels between 0.28 and 2.49 mU/L. Treatment arm 1- C is targeting a TSH level o f 5.1-12.0 mU/L
    Intervention: Drug: L-thyroxine (L-T4)
  • Experimental: 2-A
    Subjects with baseline TSH between 2.5 adn 5.0 mU/L. Treatment arm 2-A targets a THS of 0.28 -2.49 mU/L (the theoretical optimal range).
    Intervention: Drug: L-thyroxine (L-T4)
  • Experimental: 2-B
    Subjects with baseline TSH between 2.5 adn 5.0 mU/L. Treatment arm 2-B targeting a TSH of 2.5 - 5.0 mU/L
    Intervention: Drug: L-thyroxine (L-T4)
  • Experimental: 2-C
    Subjects with baseline TSH between 2.5 adn 5.0 mU/L. Treatment arm 1- C is targeting a TSH level o f 5.1-12.0 mU/L
    Intervention: Drug: L-thyroxine (L-T4)
Samuels MH, Kolobova I, Smeraglio A, Peters D, Janowsky JS, Schuff KG. The effects of levothyroxine replacement or suppressive therapy on health status, mood, and cognition. J Clin Endocrinol Metab. 2014 Mar;99(3):843-51. doi: 10.1210/jc.2013-3686. Epub 2014 Jan 13.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
324
August 2013
August 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Ages 20-75
  • Primary hypothyroidism on stable dose of L-T4 for > 3 months
  • Documented elevated TSH off L-T4
  • Normal TSH level on usual dose of L-T4
  • No acute or chronic medical or psychiatric illnesses that affect thyroid function, mood or cognition
  • No medication use that affects thyroid function, mood or cognition (oral contraceptives or estrogen therapy allowed)
  • Normal score on screening MMSE (to test for dementia)
  • Normal vision by screening examination
  • Normal hearing by screening examination
  • Non smoker

Exclusion Criteria:

  • Failure to meet any of the above inclusion criteria
  • Inability to speak and comprehend English
  • A history of coronary artery disease
  • Screening hgb <10
  • Screening wbc > 10,000
  • Clinically significant abnormalities on screening metabolic set
  • Screening LDL cholesterol > 160
  • Screening triglyceride > 300
  • Significant abnormalities on screening ECG
  • Pregnancy or intent to become pregnant in next 6 months
  • Present or recent use of medications that affect thyroid hormone levels or interfere with thyroid hormone effects, including beta-blockers, lithium, glucocorticoids, or iodine containing agents
  • MMSE score < 26
Both
20 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00565864
IRB00002265, PPQ IRB00002265
No
Mary Samuels, Oregon Health and Science University
Oregon Health and Science University
Not Provided
Principal Investigator: Mary Samuels, MD Oregon Health and Science University
Oregon Health and Science University
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP