Subclinical HypothyroidismNCT02399475

Mechanistic Study of Subclinical Hypothyroidism In the Elderly

A study testing Levothyroxine, Liothyronine and Thyrotropin-Releasing Hormone in people with Subclinical Hypothyroidism, run by University of Pennsylvania at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 70 years and older
Conditions the study is for: Subclinical Hypothyroidism
What is being tested?: Levothyroxine, Liothyronine and Thyrotropin-Releasing Hormone
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 14 participants
Where: 1 siteUnited States
Study dates: 1 Jan 2015to 30 Sep 2019
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 70 years and older
All sexes
No healthy volunteers
Older adult

Who may be able to join

men and women aged 70 and older
TSH between 4.5 and 19.9 mU/L as an outpatient
ability to provide informed consent

Who cannot join

Laboratory Tests:
TSH <4.5 mU/L or >20 mU/L on repeat testing at least four weeks later or free T4 level outside the reference range
thyroid peroxidase (TPO) antibody positive
abnormal liver function tests (LFTs >3 x upper limit of normal)
hemoglobin <11 g/dL
Surgeries or Procedures:

Show all 31Show fewer

thyroid surgery
pituitary surgery
bariatric surgery
bowel resection involving the jejunum and upper ileum
radioactive iodine therapy
radiation treatments to head or neck
Medical Conditions:
diagnosis of pituitary disease
diagnosis of amyloidosis, sarcoidosis, hemochromatosis
diagnosis of adrenal insufficiency
obesity with BMI > 35 mg/kg2
history of stroke
chronic or ongoing angina, Class II or higher congestive heart failure, or uncontrolled hypertension with current blood pressure greater than 160/100
diabetes mellitus with hemoglobin A1C level greater than 8.0% in the past six months
celiac sprue, Crohn's disease, ulcerative colitis, Zollinger-Ellison syndrome
renal insufficiency with calculated glomerular filtration rate <45 cc/min
cognitive impairment with Mini Mental State Exam[30] <24/30
history of any seizures
unstable medical or psychological condition in the judgment of the principal investigator
Medications:
thyroid hormone preparations
antithyroid drugs
medications that interfere with the absorption or metabolism of thyroid hormone
medications that interfere with the TRH stimulation test
proton pump inhibitors

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Pennsylvania
Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: The Thyroid Axis in Older Individuals With Persistent Subclinical Hypothyroidism: a Mechanistic, Randomized, Double-Blind, Cross-Over Study of Levothyroxine and Liothyronine Administration

Subclinical hypothyroidism, defined as an elevated TSH in the setting of normal thyroid hormone levels, is a common diagnosis in the elderly. The purpose of this study is to examine the hypothalamic-pituitary-thyroid axis in men and women aged 70 years and older with persistent subclinical hypothyroidism. To evaluate the mechanism behind this condition, participants will undergo thyrotropin releasing hormone stimulation testing at 3 visits: baseline and while taking two different thyroid hormone preparations, levothyroxine and liothyronine. The investigators will also assess physiologic responses to these two different thyroid hormone medications to help us understand how the thyroid works in advanced age.

Conditions: Subclinical Hypothyroidism
Being tested: Levothyroxine, Liothyronine, Thyrotropin-Releasing Hormone
Keywords: Levothyroxine, Liothyronine, Thyrotropin Releasing Hormone, Aging, Hypothyroidism, Thyroid diseases
Medical subject headings: Hypothyroidism, Thyroid Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LevothyroxineDrug
Also called Synthroid
Oral levothyroxine with a total starting dose of 0.7mcg/kg/day split into three daily doses will be titrated to a target TSH level of 0.5 -1.5mU/L
LiothyronineDrug
Also called Cytomel
Oral liothyronine with a starting dose of 1/3 of the weight-based LT4 dose divided into three daily doses titrated to a target TSH level of 0.5 -1.5mU/L
Thyrotropin-Releasing HormoneDrug
200 µg intravenous TRH will be given at study visit 1 (baseline), study visit 2 (on first thyroid treatment), and study visit 3 (on second thyroid treatment).

Study groups in NCT02399475
Study group	Role	What they receive
Levothyroxine First	Experimental	Participants will start on the thyroid hormone Levothyroxine prior to crossing over to Liothyronine Receives: Drug: Levothyroxine; Drug: Liothyronine; Drug: Thyrotropin-Releasing Hormone
Liothyronine First	Experimental	Participants will start on the thyroid hormone Liothyronine prior to crossing over to Levothyroxine Receives: Drug: Levothyroxine; Drug: Liothyronine; Drug: Thyrotropin-Releasing Hormone

What is being measured

The primary outcome is the main question the study is designed to answer.

TSH Area Under the Curve
TSH area under the curve within 60 minutes of TRH stimulation when TSH is at goal
Measured: 0, 5, 10, 15, 20, 30, and 60 min post TRH
TSH Max
The maximum concentration of TSH after TRH stimulation when TSH is at goal
Measured: Between 0 and 180 min after TRH stimulation
Free T4 Level
Free thyroxine level when TSH level is at goal on therapy.
Measured: An average of 7 months after initiating therapy
Total T3 Level
Total triiodothyronine level when TSH is at goal on therapy
Measured: An average of 7 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jan 201530 Sep 2019

First posted26 Mar 2015 (estimated)
Study start1 Jan 2015
Primary completion30 Sep 2019
Study completion30 Sep 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Subclinical 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 N/A
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02399475
Sponsor's protocol ID: 821564
Other IDs: K24AG042765-01A1
Status last verified: Feb 2021
First submitted: 3 Feb 2015
Last updated: 9 Mar 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingObservational study
Impact of Overt and Subclinical Hypothyroidism on Liver Fibrosis in Patients With MASLD
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Subclinical Hypothyroidism and Disease Activity in Rheumatoid Arthritis
Rheumatoid Arthritis, Subclinical Hypothyroidism
Not yet recruitingObservational study
Hypothyroidism and Liver Fibrosis Severity in MASLD
Metabolic Dysfunction-Associated Steatotic Liver Disease, Hypothyroidism
Not yet recruitingPhase 4
Discontinuation of Low-Dose Levothyroxine in Older Adults With Subclinical Hypothyroidism
Hypothyroidism
Recruiting
Levothyroxine Treatment on Cardiac Function in Children With Subclinical Hypothyroidism
Levothyroxine, Cardiac Function

All Subclinical Hypothyroidism trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Thyroid Axis in Older Individuals With Persistent Subclinical Hypothyroidism: a Mechanistic, Randomized, Double-Blind, Cross-Over Study of Levothyroxine and Liothyronine Administration
ClinicalTrials.gov ID: NCT02399475
Acronym / sponsor ID: 821564
Conditions: Subclinical Hypothyroidism
Keywords: Levothyroxine, Liothyronine, Thyrotropin Releasing Hormone, Aging, Hypothyroidism, Thyroid diseases
Study type: Interventional
Recruitment status: Completed
Enrolment: 14 participants (actual)
Lead sponsor: University of PennsylvaniaUniversity, hospital or other
Collaborators: National Institute on Aging (NIA)
Study start: 1 Jan 2015 (actual)
Primary completion: 30 Sep 2019 (actual)
Study completion: 30 Sep 2019 (actual)
First posted: 26 Mar 2015 (estimated)
Results: Posted 9 Mar 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Levothyroxine First	Experimental	Drug: Levothyroxine, Drug: Liothyronine, Drug: Thyrotropin-Releasing HormoneParticipants will start on the thyroid hormone Levothyroxine prior to crossing over to Liothyronine
Liothyronine First	Experimental	Drug: Levothyroxine, Drug: Liothyronine, Drug: Thyrotropin-Releasing HormoneParticipants will start on the thyroid hormone Liothyronine prior to crossing over to Levothyroxine

Who may qualify

Ages: 70 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Older adult

Key inclusion criteria (3 listed)

men and women aged 70 and older
TSH between 4.5 and 19.9 mU/L as an outpatient
ability to provide informed consent

Key exclusion criteria (31 listed)

TSH <4.5 mU/L or >20 mU/L on repeat testing at least four weeks later or free T4 level outside the reference range
thyroid peroxidase (TPO) antibody positive
abnormal liver function tests (LFTs >3 x upper limit of normal)
hemoglobin <11 g/dL
thyroid surgery

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
LevothyroxineAlso: SynthroidOral levothyroxine with a total starting dose of 0.7mcg/kg/day split into three daily doses will be titrated to a target TSH level of 0.5 -1.5mU/L	Drug	Levothyroxine First, Liothyronine First
LiothyronineAlso: CytomelOral liothyronine with a starting dose of 1/3 of the weight-based LT4 dose divided into three daily doses titrated to a target TSH level of 0.5 -1.5mU/L	Drug	Levothyroxine First, Liothyronine First
Thyrotropin-Releasing Hormone200 µg intravenous TRH will be given at study visit 1 (baseline), study visit 2 (on first thyroid treatment), and study visit 3 (on second thyroid treatment).	Drug	Levothyroxine First, Liothyronine First

Primary outcome

TSH Area Under the Curve
Time frame: 0, 5, 10, 15, 20, 30, and 60 min post TRH
TSH area under the curve within 60 minutes of TRH stimulation when TSH is at goal
TSH Max
Time frame: Between 0 and 180 min after TRH stimulation
The maximum concentration of TSH after TRH stimulation when TSH is at goal
Free T4 Level
Time frame: An average of 7 months after initiating therapy
Free thyroxine level when TSH level is at goal on therapy.
Total T3 Level
Time frame: An average of 7 months
Total triiodothyronine level when TSH is at goal on therapy

Results and safety

Results posted to the registry on 9 Mar 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Levothyroxine First	7	6
Liothyronine First	7	7

Primary outcome: TSH Area Under the Curve

Time frame: 0, 5, 10, 15, 20, 30, and 60 min post TRH. Mean (Standard Deviation). Unit: μIU*min/mL

Measure	Levothyroxine n = 13	Liothyronine n = 13
Value	267.8 (137.3)	266.2 (140.2)

Primary outcome: TSH Max

Time frame: Between 0 and 180 min after TRH stimulation. Mean (Standard Deviation). Unit: mIU/L

Measure	Levothyroxine n = 13	Liothyronine n = 13
Value	5.5 (3.0)	5.4 (2.9)

Primary outcome: Free T4 Level

Time frame: An average of 7 months after initiating therapy. Mean (Standard Deviation). Unit: ng/dL

Measure	Levothyroxine n = 13	Liothyronine n = 13
Value	1.65 (0.11)	0.46 (0.19)

Primary outcome: Total T3 Level

Time frame: An average of 7 months. Mean (Standard Deviation). Unit: ng/mL

Measure	Levothyroxine n = 13	Liothyronine n = 13
Value	1.12 (0.24)	1.98 (0.51)

Adverse events

Time frame: Through study completion, an average of 7 months in each arm. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Levothyroxine	0 of 13 (0%)	0 of 13 (0%)	0 of 13
Liothyronine	0 of 13 (0%)	0 of 13 (0%)	0 of 13

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Subclinical Hypothyroidism

Not yet recruitingObservational study
Impact of Overt and Subclinical Hypothyroidism on Liver Fibrosis in Patients With MASLD
Metabolic Dysfunction-Associated Steatotic Liver Disease, Non-Alcoholic Fatty Liver Disease
Not yet recruitingObservational study
Subclinical Hypothyroidism and Disease Activity in Rheumatoid Arthritis
Rheumatoid Arthritis, Subclinical Hypothyroidism
Not yet recruitingObservational study
Hypothyroidism and Liver Fibrosis Severity in MASLD
Metabolic Dysfunction-Associated Steatotic Liver Disease, Hypothyroidism
Not yet recruitingPhase 4
Discontinuation of Low-Dose Levothyroxine in Older Adults With Subclinical Hypothyroidism
Hypothyroidism
Recruiting
Levothyroxine Treatment on Cardiac Function in Children With Subclinical Hypothyroidism
Levothyroxine, Cardiac Function

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. This study is not recruiting at the moment.

Anne R Cappola, MD, ScM principal investigator

The 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 study testing Levothyroxine, Liothyronine and Thyrotropin-Releasing Hormone in people with Subclinical 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 3 inclusion and 31 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: finished, as of the sponsor's last update on 9 Mar 2021. 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.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

TSH Area Under the Curve (time frame: 0, 5, 10, 15, 20, 30, and 60 min post TRH). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02399475.

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 9 Mar 2021.