Dosing of LT4 in Older Individuals

Study Overview
=================
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.

Official Title
-----------------
Levothyroxine Dosing in Older Individuals

Conditions
-----------------
Hypothyroidism

Intervention / Treatment
-----------------
* Drug: Levothyroxine Sodium


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized, parallel, double-blind clinical trial of two 6-month dosing strategies of levothyroxine (LT4)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lower TSH Group<br>Target TSH level of 0.5-2.0 mU/L | Drug: Levothyroxine Sodium<br>* Levothyroxine dose will depend on dose at baseline and randomization group<br>|
| Experimental: Higher TSH group<br>Target TSH level of 5.5-7.0 mU/L | Drug: Levothyroxine Sodium<br>* Levothyroxine dose will depend on dose at baseline and randomization group<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thyroid-Related Quality of Life Patient-Reported Outcome Quality of Life scale | 22 items, scored 0-100, higher scores indicate worse status | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 6 months | 
| NIH Toolbox Fluid Cognition Composite Score | Adjusted scale score, based around median of 100, higher scores indicated higher function | 6 months | 
| Geriatric Depression Scale | 30 items, higher scores indicate more depressive symptoms | 6 months | 
| Pittsburgh Sleep Quality Index | 19 items, range of 0-21, higher scores indicate worse sleep | 6 months | 
| Weight | kilograms | 6 months | 
| LDL cholesterol | blood test, g/dL | 6 months | 
| Satisfaction with randomized status | Participants will be asked if they can guess their randomization status and satisfaction with randomization status | 6 months | 
| Beck Anxiety Inventory | Beck Anxiety Inventory, 21 items, range 0-63, higher scores indicate more anxiety | 6 months | 
| Serum c-telopeptide (CTX) | Blood test, pg/mL | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Levothyroxine Dosing