Hypothyroidism PrimaryPhase 4NCT07900737
Comparison of Two Timings of Levothyroxine Intake in Hypothyroid Patients: A Cross-over Randomized Control Trial
A Phase 4 study testing Levothyroxine Pill in people with Hypothyroidism Primary, run by Elyes Kamoun at 1 site in Tunisia.
Trial summary
Primary hypothyroidism is a common condition, affecting nearly 10% of the general population. Its treatment is levothyroxine, a synthetic thyroid hormone with a half-life of nearly eight days. Optimal absorption of levothyroxine occurs when it is taken on an empty stomach. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hypothyroidism Primary
- What is being tested?
- Levothyroxine Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 1 siteTunisia
- Study dates
- 24 Jul 2025to Dec 2026
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Primary hypothyroidism treated for at least one year
- TSH (µUI/mL) at the target with a stable levothyroxin posology for at least 6 months
Who cannot join
- Pregnant patients or patients desiring a pregnancy
- Patients having a disease responsible of a malabsorption ( coeliac disease, Crohn disease)
- End-stage organ failure ( severe chronic kidney disease, liver failure, heart failure, respiratory failure, coronary insufficiency
- Patients having a history of malignant tumor
- Patients unable to give consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Cross-over Randomised Control Trial Comparing Two Timing of Levothyroxin Intake (Fasting Versus Three Hours After Breakfast) in Well-controlled Hypothyroid Patients: Control of the Disease, Quality of Life and Satisfaction
Primary hypothyroidism is a common condition, affecting nearly 10% of the general population. Its treatment is levothyroxine, a synthetic thyroid hormone with a half-life of nearly eight days. Optimal absorption of levothyroxine occurs when it is taken on an empty stomach. It is generally recommended to take the medication in the morning, at least 30 minutes before breakfast. However, this treatment regimen can be challenging for some patients. Missed doses constitute a problem, leading some patients to choose another timing of intake. Other patients may find it difficult to wait before breakfast, resulting in suboptimal absorption, increased TSH levels, and poor disease control.
Despite these challenges, American Thyroid Association guidelines recommend taking levothyroxine in the morning, in a fasting state, as the preferred timing of intake. They also suggest bedtime intake as a reasonable alternative, as long as the medication is taken at least three hours after the evening meal. As optimal levothyroxine absorption depends primarily on intake on an empty stomach, alternative treatment schedules could be considered, as long as the fasting requirement is respected to maintain stable TSH levels.
Read more
To our knowledge, only one study has compared daytime levothyroxine intake, three hours after breakfast, with morning and bedtime intake. There was no significant difference in TSH levels between the different schedules. Confirming the stability of TSH levels with different schedules would offer patients with hypothyroidism greater flexibility in treatment timing, better adapted to their lifestyle habits.
The aim of our study is to compare serum TSH levels according to two timings of levothyroxine intake in patients with hypothyroidism. Secondary objectives are to assess treatment adherence, quality of life, and patients' preferred timing of levothyroxine intake.
- Conditions
- Hypothyroidism Primary
- Being tested
- Levothyroxine Pill
- Keywords
- hypothyroidism, Thyroxine, patient compliance
- Medical subject headings
- Hypothyroidism, Patient Compliance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Levothyroxine PillDrug
Levothyroxine will be taken in a fasting state in the morning, with a waiting time of at least 30 minutes before breakfast. TSH levels will be measured after eight weeks. There will be no washout period. During the second period, levothyroxine will be taken three hours after breakfast, with at least 30 minutes before any further oral intake. TSH levels will be measured after eight weeks.
Levothyroxine PillDrug
Levothyroxine will be taken three hours after breakfast, with at least 30 minutes before any further oral intake. TSH levels will be measured after eight weeks. There will be no washout period. During the second period, levothyroxine will be taken in a fasting state in the morning, with a waiting time of at least 30 minutes before breakfast. TSH levels will be measured after eight weeks.
| Study group | Role | What they receive |
|---|---|---|
| Levothyroxine intake before breakfast firstly, levothyroxine intake 3 hours after breakfast secondly | Active comparator | In this group, during the first period, patients will take levothyroxine in a fasting state and then wait at least 30 minutes before eating. TSH levels will be measured after eight weeks, with assessment of adherence, satisfaction, and quality of life. During the second period, patients will take levothyroxine three hours after breakfast and avoid eating anything else for at least 30 minutes. TSH levels will be measured after eight weeks, with assessment of adherence, satisfaction, and quality of life. After completion of the two periods, the investigators will ask patients about their preferred timing of levothyroxine intake. Other medications must be taken at least three hours after levothyroxine intake. Receives: Drug: Levothyroxine Pill |
| Levothyroxine intake 3 hour after breakfast firstly, levothyroxine intake before breakfast secondly | Active comparator | In this group, during the first period, patients will take levothyroxine three hours after breakfast and avoid eating anything else for at least 30 minutes. TSH levels will be measured after eight weeks, with assessment of adherence, satisfaction, and quality of life. During the second period, patients will take levothyroxine in a fasting state and then wait at least 30 minutes before eating. TSH levels will be measured after eight weeks, with assessment of adherence, satisfaction, and quality of life. After completion of the two periods, the investigators will ask patients about their preferred timing of levothyroxine intake. Other medications must be taken at least three hours after levothyroxine intake. Receives: Drug: Levothyroxine Pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stability of TSH levels with both timing of intake
The primary outcome is to compare TSH levels when levothyroxine is taken at fasting, and TSH levels (µUI/mL) when levothyroxine is taken three hours after breakfast. The investigators aim to confirm that TSH levels (µUI/mL)won't change despite the change of timing of intake, and TSH levels (µUI/mL) will be comparable in either group, i.e no significant difference of TSH levels (µUI/mL) regardless of the first arm of levothyroxin intake
Measured: From enrollment to 16 weeks after enrollment, with two TSH performed for each patient with a 8 weeks interval
Secondary outcomes (1)
Girerd scale adherence and Likert satisfaction scale to change of timing of intake
The investigators aim to determine for each patient the adherence to each timing of intake, for a better statistical analysis and to assess wether the timing of intake affects the adherence. The adherence will be be determined using the Girerd scale, which is a six-item questionnaire from 0 to 6 points. A score of zero means a good adherence, a score of 1 or 2 means a moderate adherence, and a score of 3 and above means a poor adherence. The investigators will also determine the satisfaction using a Likert satisfaction scale ranging from 1 to 5, with 1 meaning very dissatisfied and 5 meaning very satisfied. This determination will be made after each timing to determine, at the end of the study, which timing was preferred by the enrolled patients
Measured: from enrollment to 16 weeks after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2026
- Study start24 Jul 2025
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypothyroidism PrimaryStudies of the same condition, open and under way.
- 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
- Crossover
- Masking
- None (open label)
- Enrolment
- 102 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Elyes Kamoun
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Elyes Kamoun, University Tunis El Manar
- Investigators
- Melika Chihaoui, Medical professor, Study director, University Tunis El Manar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07900737
- Sponsor's protocol ID
- 23/2025
- Status last verified
- Oct 2026
- First submitted
- 17 Sep 2025
- Last updated
- 28 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The investigators will share data regarding the study protocol, the consent form, the arms of study and the primary and secondary outcomes
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Cross-over Randomised Control Trial Comparing Two Timing of Levothyroxin Intake (Fasting Versus Three Hours After Breakfast) in Well-controlled Hypothyroid Patients: Control of the Disease, Quality of Life and Satisfaction
- ClinicalTrials.gov ID
- NCT07900737
- Acronym / sponsor ID
- 23/2025
- Conditions
- Hypothyroidism Primary
- Keywords
- hypothyroidism, Thyroxine, patient compliance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 102 participants (estimated)
- Lead sponsor
- Elyes KamounUniversity, hospital or other
- Study start
- 24 Jul 2025 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 28 Oct 2026 (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.
Primary hypothyroidism is a common condition, affecting nearly 10% of the general population. Its treatment is levothyroxine, a synthetic thyroid hormone with a half-life of nearly eight days. Optimal absorption of levothyroxine occurs when it is taken on an empty stomach. It is generally recommended to take the medication in the morning, at least 30 minutes before breakfast. However, this treatment regimen can be challenging for some patients. Missed doses constitute a problem, leading some patients to choose another timing of intake. Other patients may find it difficult to wait before breakfast, resulting in suboptimal absorption, increased TSH levels, and poor disease control.
Despite these challenges, American Thyroid Association guidelines recommend taking levothyroxine in the morning, in a fasting state, as the preferred timing of intake. They also suggest bedtime intake as a reasonable alternative, as long as the medication is taken at least three hours after the evening meal. As optimal levothyroxine absorption depends primarily on intake on an empty stomach, alternative treatment schedules could be considered, as long as the fasting requirement is respected to maintain stable TSH levels.
To our knowledge, only one study has compared daytime levothyroxine intake, three hours after breakfast, with morning and bedtime intake. There was no significant difference in TSH levels between the different schedules. Confirming the stability of TSH levels with different schedules would offer patients with hypothyroidism greater flexibility in treatment timing, better adapted to their lifestyle habits.
The aim of our study is to compare serum TSH levels according to two timings of levothyroxine intake in patients with hypothyroidism. Secondary objectives are to assess treatment adherence, quality of life, and patients' preferred timing of levothyroxine intake.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Levothyroxine intake before breakfast firstly, levothyroxine intake 3 hours after breakfast secondly | Active comparator | Drug: Levothyroxine PillIn this group, during the first period, patients will take levothyroxine in a fasting state and then wait at least 30 minutes before eating. TSH levels will be measured after eight weeks, with assessment of adherence, satisfaction, and quality of life. During the second period, patients will take levothyroxine three hours after breakfast and avoid eating anything else for at least 30 minutes. TSH levels will be measured after eight weeks, with assessment of adherence, satisfaction, and quality of life. After completion of the two periods, the investigators will ask patients about their preferred timing of levothyroxine intake. Other medications must be taken at least three hours after levothyroxine intake. |
| Levothyroxine intake 3 hour after breakfast firstly, levothyroxine intake before breakfast secondly | Active comparator | Drug: Levothyroxine PillIn this group, during the first period, patients will take levothyroxine three hours after breakfast and avoid eating anything else for at least 30 minutes. TSH levels will be measured after eight weeks, with assessment of adherence, satisfaction, and quality of life. During the second period, patients will take levothyroxine in a fasting state and then wait at least 30 minutes before eating. TSH levels will be measured after eight weeks, with assessment of adherence, satisfaction, and quality of life. After completion of the two periods, the investigators will ask patients about their preferred timing of levothyroxine intake. Other medications must be taken at least three hours after levothyroxine intake. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Primary hypothyroidism treated for at least one year
- TSH (µUI/mL) at the target with a stable levothyroxin posology for at least 6 months
Key exclusion criteria (5 listed)
- Pregnant patients or patients desiring a pregnancy
- Patients having a disease responsible of a malabsorption ( coeliac disease, Crohn disease)
- End-stage organ failure ( severe chronic kidney disease, liver failure, heart failure, respiratory failure, coronary insufficiency
- Patients having a history of malignant tumor
- Patients unable to give consent
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 PillLevothyroxine will be taken in a fasting state in the morning, with a waiting time of at least 30 minutes before breakfast. TSH levels will be measured after eight weeks. There will be no washout period. During the second period, levothyroxine will be taken three hours after breakfast, with at least 30 minutes before any further oral intake. TSH levels will be measured after eight weeks. | Drug | Levothyroxine intake before breakfast firstly, levothyroxine intake 3 hours after breakfast secondly |
| Levothyroxine PillLevothyroxine will be taken three hours after breakfast, with at least 30 minutes before any further oral intake. TSH levels will be measured after eight weeks. There will be no washout period. During the second period, levothyroxine will be taken in a fasting state in the morning, with a waiting time of at least 30 minutes before breakfast. TSH levels will be measured after eight weeks. | Drug | Levothyroxine intake 3 hour after breakfast firstly, levothyroxine intake before breakfast secondly |
Primary outcome
Stability of TSH levels with both timing of intake
Time frame: From enrollment to 16 weeks after enrollment, with two TSH performed for each patient with a 8 weeks interval
The primary outcome is to compare TSH levels when levothyroxine is taken at fasting, and TSH levels (µUI/mL) when levothyroxine is taken three hours after breakfast. The investigators aim to confirm that TSH levels (µUI/mL)won't change despite the change of timing of intake, and TSH levels (µUI/mL) will be comparable in either group, i.e no significant difference of TSH levels (µUI/mL) regardless of the first arm of levothyroxin intake
1 secondary outcome
Girerd scale adherence and Likert satisfaction scale to change of timing of intake
Time frame: from enrollment to 16 weeks after enrollment
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 28 Oct 2026.
- Individual participant dataSharing planned: Yes. The investigators will share data regarding the study protocol, the consent form, the arms of study and the primary and secondary outcomes
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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. This study is not recruiting at the moment.
Melika Chihaoui, Medical professor study director
University Tunis El Manar
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 Pill in people with Hypothyroidism Primary, run by Elyes Kamoun at 1 site in Tunisia.
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 2 inclusion and 5 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: under way, not looking for participants, as of the sponsor's last update on 28 Oct 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 Tunisia. 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?
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?
Stability of TSH levels with both timing of intake (time frame: From enrollment to 16 weeks after enrollment, with two TSH performed for each patient with a 8 weeks interval). 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 28 Oct 2026.