Dosing of LT4 in Older Individuals

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified January 2026 by University of Pennsylvania
Sponsor
University of Pennsylvania
Information Provided by (Responsible Party)
Anne Cappola, MD
Clinicaltrials.gov Identifier
NCT06073665
Other Study ID Numbers:
1R01AG081698-01, #853300
First Submitted
September 21, 2023
First Posted
October 9, 2023
Last Update Posted
February 18, 2026
Last Verified
January 2026

ClinicalTrials.gov processed this data on February 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Investigators will perform a randomized, parallel, double-blind clinical trial of two 6-month dosing strategies of levothyroxine (LT4) in patients aged 65 years and older who are already taking a stable dose of at least 1.2 mcg/kg/day of LT4 therapy, one to maintain a target thyroid stimulating hormone (TSH) level of 0.5-2.0 mU/L (lower TSH group) and another of a lower levothyroxine dose to achieve a target TSH of 5.5-7.0 mU/L (higher TSH group). Investigators will assess the effects of levothyroxine therapy at two different TSH targets on symptoms of hypothyroidism, mood, sleep, measures of memory and executive function, weight, lipids, and a marker of bone turnover.

Condition or DiseaseIntervention/Treatment
Hypothyroidism
Drug: Levothyroxine SodiumDrug: Levothyroxine Sodium

Study Design

Study TypeInterventional
Actual Enrollment228 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleLevothyroxine Dosing in Older Individuals
Study Start DateJanuary 30, 2024
Actual Primary Completion Date1yr 10mos from now
Actual Study Completion Date1yr 10mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Lower TSH Group
Target TSH level of 0.5-2.0 mU/L
Drug: Levothyroxine Sodium
Levothyroxine dose will depend on dose at baseline and randomization group
Higher TSH group
Target TSH level of 5.5-7.0 mU/L
Drug: Levothyroxine Sodium
Levothyroxine dose will depend on dose at baseline and randomization group

Outcome Measures

Primary Outcome Measures
  1. Thyroid-Related Quality of Life Patient-Reported Outcome Quality of Life scale
    22 items, scored 0-100, higher scores indicate worse status
Secondary Outcome Measures
  1. Thyroid-Related Quality of Life Patient-Reported Outcome Hypothyroidism subscale b. ThyPRO "Tiredness" subscale c. Thyroid Symptoms Questionnaire (TSQ)
    4 items, scored 0-100, higher scores indicate worse status
  2. NIH Toolbox Fluid Cognition Composite Score
    Adjusted scale score, based around median of 100, higher scores indicated higher function
  3. Geriatric Depression Scale
    30 items, higher scores indicate more depressive symptoms
  4. Pittsburgh Sleep Quality Index
    19 items, range of 0-21, higher scores indicate worse sleep
  5. Weight
    kilograms
  6. LDL cholesterol
    blood test, g/dL
  7. Satisfaction with randomized status
    Participants will be asked if they can guess their randomization status and satisfaction with randomization status
  8. Beck Anxiety Inventory
    Beck Anxiety Inventory, 21 items, range 0-63, higher scores indicate more anxiety
  9. Serum c-telopeptide (CTX)
    Blood test, pg/mL

Eligibility Criteria

Ages Eligible for Study(Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
1. Provision of signed and dated informed consent form 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. Male or female, community dwelling, aged 65 years or older 4. Diagnosed with hypothyroidism of any etiology for at least 6 months, taking 75-200 mcg per day LT4 and a minimum of 1.2 mcg/kg/day with no dose adjustment since the last TSH test. 5. Ability to take oral medication and be willing to adhere to the medication regimen 6. Adherence to lifestyle considerations.
Exclusion Criteria
1. Hypopituitarism 2. History of thyroid cancer requiring suppression of TSH secretion 3. Current use of liothyronine (LT3), thyroid extracts, Tirosint liquid or capsules, and medications that interfere with thyroid function or thyroid function tests 4. GFR \<30 ml/min/1.73 m2 within the prior 12 months 5. Unable to understand and comply with study requirements, as assessed by study staff and the PI, will be excluded. 6. Other conditions which, in the opinion of the investigators, would prevent them from participating in the full duration of the study. 7. Currently taking multikinase or checkpoint inhibitor therapy. 8. Any history of food dye allergy.

Contacts and Locations

Sponsors and CollaboratorsUniversity of Pennsylvania
Locations
Penn Medicine, Smilow Translational Research Center | Philadelphia Pennsylvania, United States, 19104
Investigators
Principal Investigator: Anne R. Cappola, M.D., Sc.M., University of Pennsylvania