DOT4: Dosing of LT4 in Older Individuals

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06073665
• Collaborator: National Institute on Aging (NIA) (NIH)
• Enrollment: 228
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 54
• Patients Per Site Per Month: 4.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Hypothyroidism	Drug: Levothyroxine Sodium	Phase 4

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

• Study Type: Interventional
• Anticipated Enrollment: 228 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: randomized, parallel, double-blind clinical trial of two 6-month dosing strategies of levothyroxine (LT4)randomized, parallel, double-blind clinical trial of two 6-month dosing strategies of levothyroxine (LT4)
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: overencapsulated levothyroxine doses will be provided by the investigational drug pharmacy
• Primary Purpose: Treatment
• Official Title: Levothyroxine Dosing in Older Individuals
• Anticipated Study Start Date: Oct 1, 2023
• Anticipated Primary Completion Date: Apr 1, 2028
• Anticipated Study Completion Date: Apr 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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
Experimental: 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 [6 months]

   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) [6 months]

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

2. NIH Toolbox Fluid Cognition Composite Score [6 months]

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

3. Geriatric Depression Scale [6 months]

   30 items, higher scores indicate more depressive symptoms

4. Pittsburgh Sleep Quality Index [6 months]

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

5. Weight [6 months]

   kilograms

6. LDL cholesterol [6 months]

   blood test, g/dL

7. Satisfaction with randomized status [6 months]

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

8. Beck Anxiety Inventory [6 months]

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

9. Serum c-telopeptide (CTX) [6 months]

   Blood test, pg/mL

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Penn Medicine, Smilow Translational Research Center	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania
• National Institute on Aging (NIA)

Investigators

• Principal Investigator: Anne R. Cappola, M.D., Sc.M., University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Anne Cappola, MD, Professor of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT06073665
• Other Study ID Numbers: 1R01AG081698-01; R01AG081698
• First Posted: Oct 10, 2023
• Last Update Posted: Oct 10, 2023
• Last Verified: Oct 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Anne Cappola, MD, Professor of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania: Levothyroxine Dosing
• Additional relevant MeSH terms: Hypothyroidism

Study Results

No Results Posted as of Oct 10, 2023