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Dosing of LT4 in Older Individuals (DOT4)

Primary Purpose

Hypothyroidism

Status
Not yet recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Levothyroxine Sodium
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypothyroidism focused on measuring Levothyroxine Dosing

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

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 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.

Sites / Locations

  • Penn Medicine, Smilow Translational Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Lower TSH Group

Higher TSH group

Arm Description

Target TSH level of 0.5-2.0 mU/L

Target TSH level of 5.5-7.0 mU/L

Outcomes

Primary Outcome Measures

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

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
NIH Toolbox Fluid Cognition Composite Score
Adjusted scale score, based around median of 100, higher scores indicated higher function
Geriatric Depression Scale
30 items, higher scores indicate more depressive symptoms
Pittsburgh Sleep Quality Index
19 items, range of 0-21, higher scores indicate worse sleep
Weight
kilograms
LDL cholesterol
blood test, g/dL
Satisfaction with randomized status
Participants will be asked if they can guess their randomization status and satisfaction with randomization status
Beck Anxiety Inventory
Beck Anxiety Inventory, 21 items, range 0-63, higher scores indicate more anxiety
Serum c-telopeptide (CTX)
Blood test, pg/mL

Full Information

First Posted
September 22, 2023
Last Updated
October 23, 2023
Sponsor
University of Pennsylvania
Collaborators
National Institute on Aging (NIA)
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1. Study Identification

Unique Protocol Identification Number
NCT06073665
Brief Title
Dosing of LT4 in Older Individuals
Acronym
DOT4
Official Title
Levothyroxine Dosing in Older Individuals
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 15, 2023 (Anticipated)
Primary Completion Date
April 1, 2028 (Anticipated)
Study Completion Date
April 1, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pennsylvania
Collaborators
National Institute on Aging (NIA)

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypothyroidism
Keywords
Levothyroxine Dosing

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
randomized, parallel, double-blind clinical trial of two 6-month dosing strategies of levothyroxine (LT4)
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
overencapsulated levothyroxine doses will be provided by the investigational drug pharmacy
Allocation
Randomized
Enrollment
228 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Lower TSH Group
Arm Type
Active Comparator
Arm Description
Target TSH level of 0.5-2.0 mU/L
Arm Title
Higher TSH group
Arm Type
Experimental
Arm Description
Target TSH level of 5.5-7.0 mU/L
Intervention Type
Drug
Intervention Name(s)
Levothyroxine Sodium
Intervention Description
Levothyroxine dose will depend on dose at baseline and randomization group
Primary Outcome Measure Information:
Title
Thyroid-Related Quality of Life Patient-Reported Outcome Quality of Life scale
Description
22 items, scored 0-100, higher scores indicate worse status
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Thyroid-Related Quality of Life Patient-Reported Outcome Hypothyroidism subscale b. ThyPRO "Tiredness" subscale c. Thyroid Symptoms Questionnaire (TSQ)
Description
4 items, scored 0-100, higher scores indicate worse status
Time Frame
6 months
Title
NIH Toolbox Fluid Cognition Composite Score
Description
Adjusted scale score, based around median of 100, higher scores indicated higher function
Time Frame
6 months
Title
Geriatric Depression Scale
Description
30 items, higher scores indicate more depressive symptoms
Time Frame
6 months
Title
Pittsburgh Sleep Quality Index
Description
19 items, range of 0-21, higher scores indicate worse sleep
Time Frame
6 months
Title
Weight
Description
kilograms
Time Frame
6 months
Title
LDL cholesterol
Description
blood test, g/dL
Time Frame
6 months
Title
Satisfaction with randomized status
Description
Participants will be asked if they can guess their randomization status and satisfaction with randomization status
Time Frame
6 months
Title
Beck Anxiety Inventory
Description
Beck Anxiety Inventory, 21 items, range 0-63, higher scores indicate more anxiety
Time Frame
6 months
Title
Serum c-telopeptide (CTX)
Description
Blood test, pg/mL
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anne R. Cappola, M.D., Sc.M.
Phone
215-573-5359
Email
acappola@pennmedicine.upenn.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Theresa M. Scattergood, M.S.N., R.N.
Phone
215-898-5664
Email
theresa.scattergood@pennmedicine.upenn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne R. Cappola, M.D., Sc.M.
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
Penn Medicine, Smilow Translational Research Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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