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
  Purpose

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.


Condition Intervention
Hypothyroidism
Drug: L-thyroxine (L-T4)

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Neurocognitive and Metabolic Effects of Mild Hypothyroidism

Resource links provided by NLM:


Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 324
Study Start Date: August 2008
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
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-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
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-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
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: 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).
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: 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
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: 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
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.

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00565864

Locations
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97201
Sponsors and Collaborators
Oregon Health and Science University
Investigators
Principal Investigator: Mary Samuels, MD Oregon Health and Science University
  More Information

No publications provided by Oregon Health and Science University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mary Samuels, Professor of Medicine, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT00565864     History of Changes
Other Study ID Numbers: IRB00002265, PPQ IRB00002265
Study First Received: November 28, 2007
Last Updated: November 7, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Oregon Health and Science University:
Hypothyroidism
Cognition
Metabolism

Additional relevant MeSH terms:
Hypothyroidism
Thyroid Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on August 28, 2014