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Recruiting

NCT Number: NCT06073665

Dosing of LT4 in Older Individuals

Our overall goal is to determine the clinical consequences of allowing greater flexibility in LT4 dosing in older individuals who take LT4.

Recruiting

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Key information

Age range

65 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Penn Medicine, Smilow Translational Research Center

Philadelphia, Pennsylvania, 19104, United States

Location status: Recruiting

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Provision of signed and dated informed consent form
  • Stated willingness to comply with all study procedures and availability for the duration of the study
  • Male or female, community dwelling, aged 65 years or older
  • 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.
  • Ability to take oral medication and be willing to adhere to the medication regimen
  • Adherence to lifestyle considerations.

Exclusion criteria

  • Hypopituitarism
  • History of thyroid cancer requiring suppression of TSH secretion
  • Current use of liothyronine (LT3), thyroid extracts, Tirosint liquid or capsules, and medications that interfere with thyroid function or thyroid function tests
  • GFR <30 ml/min/1.73 m2 within the prior 12 months
  • Unable to understand and comply with study requirements, as assessed by study staff and the PI, will be excluded.
  • Other conditions which, in the opinion of the investigators, would prevent them from participating in the full duration of the study.
  • Currently taking multikinase or checkpoint inhibitor therapy.
  • Any history of food dye allergy.

Treatment and study plan

Levothyroxine Sodium

Drug

Levothyroxine dose will depend on dose at baseline and randomization group

Primary outcomes

  1. Thyroid-Related Quality of Life Patient-Reported Outcome Quality of Life scale

    Time frame: 6 months

    22 items, scored 0-100, higher scores indicate worse status

Secondary outcomes

  1. Thyroid-Related Quality of Life Patient-Reported Outcome Hypothyroidism subscale b. ThyPRO "Tiredness" subscale c. Thyroid Symptoms Questionnaire (TSQ)

    Time frame: 6 months

    4 items, scored 0-100, higher scores indicate worse status

  2. NIH Toolbox Fluid Cognition Composite Score

    Time frame: 6 months

    Adjusted scale score, based around median of 100, higher scores indicated higher function

  3. Geriatric Depression Scale

    Time frame: 6 months

    30 items, higher scores indicate more depressive symptoms

  4. Pittsburgh Sleep Quality Index

    Time frame: 6 months

    19 items, range of 0-21, higher scores indicate worse sleep

  5. Weight

    Time frame: 6 months

    kilograms

  6. LDL cholesterol

    Time frame: 6 months

    blood test, g/dL

  7. Satisfaction with randomized status

    Time frame: 6 months

    Participants will be asked if they can guess their randomization status and satisfaction with randomization status

  8. Beck Anxiety Inventory

    Time frame: 6 months

    Beck Anxiety Inventory, 21 items, range 0-63, higher scores indicate more anxiety

  9. Serum c-telopeptide (CTX)

    Time frame: 6 months

    Blood test, pg/mL

Study contacts

Contact information is provided by the study sponsor or research team.

Anne R. Cappola, M.D., Sc.M.

CONTACT

[email protected]

215-573-5359

Theresa M. Scattergood, M.S.N., R.N.

CONTACT

[email protected]

215-898-9275

Sponsors and collaborators

Lead sponsor

University of Pennsylvania

Other

Collaborators

  • National Institute on Aging (NIA)

Registry information

Official study title

Levothyroxine Dosing in Older Individuals

Acronym: DOT4

Important dates

Study start
2024
Primary completion
2028
Study completion
2028
First posted
Oct 10, 2023
Registry last updated
Feb 19, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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