HypothyroidismPhase 4DOT4NCT06073665
Dosing of LT4 in Older Individuals
A Phase 4 study testing Levothyroxine Sodium in people with Hypothyroidism, run by University of Pennsylvania at 1 site in United States.
Trial summary
Our overall goal is to determine the clinical consequences of allowing greater flexibility in LT4 dosing in older individuals who take LT4. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Hypothyroidism
- What is being tested?
- Levothyroxine Sodium
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 228 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jan 2024to 1 Apr 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Penn Medicine, Smilow Translational Research Center
Philadelphia, Pennsylvania, 19104
About this study
Official title: Levothyroxine Dosing 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.
Read the detailed 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.
- Conditions
- Hypothyroidism
- Being tested
- Levothyroxine Sodium
- Keywords
- Levothyroxine Dosing
- Medical subject headings
- Hypothyroidism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Levothyroxine SodiumDrug
Levothyroxine dose will depend on dose at baseline and randomization group
| Study group | Role | What they receive |
|---|---|---|
| Lower TSH Group | Active comparator | Target TSH level of 0.5-2.0 mU/L Receives: Drug: Levothyroxine Sodium |
| Higher TSH group | Experimental | Target TSH level of 5.5-7.0 mU/L Receives: Drug: Levothyroxine Sodium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Thyroid-Related Quality of Life Patient-Reported Outcome Quality of Life scale
22 items, scored 0-100, higher scores indicate worse status
Measured: 6 months
Secondary outcomes (9)
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
Measured: 6 months
NIH Toolbox Fluid Cognition Composite Score
Adjusted scale score, based around median of 100, higher scores indicated higher function
Measured: 6 months
Geriatric Depression Scale
30 items, higher scores indicate more depressive symptoms
Measured: 6 months
Pittsburgh Sleep Quality Index
19 items, range of 0-21, higher scores indicate worse sleep
Measured: 6 months
Weight
kilograms
Measured: 6 months
LDL cholesterol
blood test, g/dL
Measured: 6 months
Satisfaction with randomized status
Participants will be asked if they can guess their randomization status and satisfaction with randomization status
Measured: 6 months
Beck Anxiety Inventory
Beck Anxiety Inventory, 21 items, range 0-63, higher scores indicate more anxiety
Measured: 6 months
Serum c-telopeptide (CTX)
Blood test, pg/mL
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2023
- Study start31 Jan 2024
- Primary completion1 Apr 2028 (estimated)
- Study completion1 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypothyroidismStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized, parallel, double-blind clinical trial of two 6-month dosing strategies of levothyroxine (LT4)
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 228 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Anne Cappola, MD, University of Pennsylvania
- Investigators
- Anne R. Cappola, M.D., Sc.M., Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06073665
- Sponsor's protocol ID
- 1R01AG081698-01, #853300
- Other IDs
- R01AG081698
- Acronym
- DOT4
- Status last verified
- Feb 2026
- First submitted
- 22 Sep 2023
- Last updated
- 19 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Levothyroxine Dosing in Older Individuals
- ClinicalTrials.gov ID
- NCT06073665
- Acronym / sponsor ID
- DOT4 / 1R01AG081698-01, #853300
- Conditions
- Hypothyroidism
- Keywords
- Levothyroxine Dosing
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 228 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 31 Jan 2024 (actual)
- Primary completion
- 1 Apr 2028 (estimated)
- Study completion
- 1 Apr 2028 (estimated)
- First posted
- 10 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Our overall goal is to determine the clinical consequences of allowing greater flexibility in LT4 dosing in older individuals who take LT4.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- randomized, parallel, double-blind clinical trial of two 6-month dosing strategies of levothyroxine (LT4)
| Arm | Type | Receives |
|---|---|---|
| Lower TSH Group | Active comparator | Drug: Levothyroxine SodiumTarget TSH level of 0.5-2.0 mU/L |
| Higher TSH group | Experimental | Drug: Levothyroxine SodiumTarget TSH level of 5.5-7.0 mU/L |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Levothyroxine SodiumLevothyroxine dose will depend on dose at baseline and randomization group | Drug | Higher TSH group, Lower TSH Group |
Primary outcome
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
9 secondary outcomes
Thyroid-Related Quality of Life Patient-Reported Outcome Hypothyroidism subscale b. ThyPRO "Tiredness" subscale c. Thyroid Symptoms Questionnaire (TSQ)
Time frame: 6 months
NIH Toolbox Fluid Cognition Composite Score
Time frame: 6 months
Geriatric Depression Scale
Time frame: 6 months
Pittsburgh Sleep Quality Index
Time frame: 6 months
Weight
Time frame: 6 months
LDL cholesterol
Time frame: 6 months
Satisfaction with randomized status
Time frame: 6 months
Beck Anxiety Inventory
Time frame: 6 months
Serum c-telopeptide (CTX)
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Anne R. Cappola, M.D., Sc.M. principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Levothyroxine Sodium in people with Hypothyroidism, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anne R. Cappola, M.D., Sc.M. (215-573-5359, acappola@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Thyroid-Related Quality of Life Patient-Reported Outcome Quality of Life scale (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2026.