Drug interaction study with thyroid hormone and magnesium preparation in healthy volunteers
| ISRCTN | ISRCTN18075783 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18075783 |
| Secondary identifying numbers | 2.1 |
- Submission date
- 16/10/2023
- Registration date
- 17/10/2023
- Last edited
- 17/10/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English Summary
Background and study aims
Levothyroxine is a medication commonly taken with products that have certain types of minerals like calcium. When you take it with calcium, it can make your body absorb less of the levothyroxine. However, we don't have any information yet about how magnesium, which is also a similar kind of mineral, affects the absorption of levothyroxine. It's very possible that magnesium might also have an impact on how your body takes in levothyroxine. So, the aim of this study is to figure out how much magnesium affects the absorption of levothyroxine.
Who can participate?
Participants are healthy volunteers aged 18-65 years who have signed the informed consent form.
What does the study involve?
After giving initial information either in person or over the phone and signing the informed consent form, a comprehensive medical history is taken, along with a physical examination. Blood samples are collected to check certain factors that help determine if participants can participate in the study or not. If they meet all the requirements to join the study and don't have any factors that exclude them, they are randomly assigned to one of three groups: one that takes levothyroxine by itself, one that takes levothyroxine with Magnesium Citrate, and one that takes levothyroxine with Magnesium Aspartate.
During each of these administrations, we measure Thyroxin levels at a total of 6 different time points. This helps us calculate and compare the area under the curve (AUC) for Thyroxin. To make the process more comfortable and avoid multiple needle pricks during each visit, we use a catheter in the vein to draw blood. The duration of the visits can vary. The information session typically lasts 20-30 minutes, the screening phase takes about 30-60 minutes, and the following three visits each last around 6.5 hours.
All these visits need to happen within a 6-month period, and there should be at least 4 weeks between visits 3, 4, and 5 to ensure that any remaining medication from the previous visit doesn't affect the results
What are the possible benefits and risks of participating?
The participation has no direct advantage for the participants. Potential risks mainly concern the levothyroxine-sodium, since a higher dose than the one described in the prescription drug information is taken. Potential adverse effects of levothyroxine like insomnia, nervousness, diarrhea, tremor, diaphoresis, headache, tachycardia, dysrhythmias and angina pectoris cannot be excluded. But these are expected to be mild and transient in nature. Since there are only three doses of levothyroxine administered, the negative impact on the subjects is expected to be minimal. The administration of two standard doses in total of magnesium preparations are not likely to pose a significant risk to subjects, the potential adverse event of soft stool/diarrhea is unlikely after one dose and transient as well.
Where is the study run from?
University Hospital of Zurich (Switzerland)
When is the study starting and how long is it expected to run for?
March 2023 to December 2024
Who is funding the study?
University of Zurich (Switzerland)
Who is the main contact?
Dr Jérôme Bonzon, jerome.bonzon@usz.ch
Contact information
Public, Scientific, Principal Investigator
Rämistrasse 100
Zürich
8091
Switzerland
 ORCID ID |
0000-0003-0195-0115 |
|---|---|
| Phone | +41 (0)442554074 |
| jerome.bonzon@usz.ch |
Study information
| Study design | Open-label drug-drug-interaction study with cross-over design |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Hospital |
| Study type | Safety |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet. |
| Scientific title | Single Centre Drug-Drug Interaction study with Levothyroxine/Magnesium-Citrate and Levothyroxine/Magnesium-Aspartate in healthy subjects |
| Study acronym | ThyroMag |
| Study hypothesis | The two treatments with a magnesium compound will reduce the AUC of thyroxine compared to levothyroxine alone, but no difference is expected between the combination of levothyroxine with magnesium-citrate vs. magnesium-aspartate. The null hypothesis is that the three treatments do not differ regarding the AUC of thyroxine. |
| Ethics approval(s) |
Approved 06/10/2023, Kantonale Ethikkommission Zürich (Stampfenbachstrasse 121, Zürich, 8090, Switzerland; +41 43 259 79 69; admin.kek@kek.zh), ref: 2023-01493 |
| Condition | Hypothyroidism |
| Intervention | Cross-over study with three groups. Each of the three treatments is during only 360 minutes: The time required to take the blood samples. A wash-out phase of min. 4 weeks is planned between each treatment. No specific follow-up is planned. Group 1: One dose of Magnesium-Aspartate (10 mmol) in powder form, taken orally along with levothyroxine 1 mg Group 2: One dose of Magnesium-Citrate (300 mg) in powder form, taken orally along with levothyroxine 1 mg, compared to Group 3: One dose of levothyroxine 1 mg alone Randomization: Due to the cross-over design of the trial, subjects will receive all treatments. The subjects will be block-randomized to three different treatment sequences in a 1:1:1 fashion with a block size of 6. Treatment sequences are chosen to ensure that each treatment appears once in each position (1st, 2nd, 3rd), ABC, BCA and CAB, A being levothyroxine alone, B being levothyroxine + magnesium citrate and C being levothyroxine + magnesium aspartate. The randomization list is prepared in advance by the trial statistician, and allocation concealment will be handled via sequentially numbered, opaque and sealed envelopes by a person at the study center that is not involved in the trial. Only after sealing, the envelopes are handed to the investigators. After inclusion of a participant, the four-digit-number assigned to the participant is written in wet ink on the envelope, before the seal is broken. The envelopes are opened according to their sequential number. Should a participant decide to terminate the study early, the sequences are re-used after all envelopes have been used up (for the 13th participant who replaces the participant that did not complete all visits). |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Euthyrox® (Levothyroxin-Natrium), Magnesiocard® (Magnesium-Aspartat) 10 mmol, Magnesium Diasporal® (Magnesium-Citrat) 300 mg |
| Primary outcome measure | AUC of total thyroxin in the serum up to 6 hours after ingestion of levothyroxine, with measurements at 0 min, 30 min, 60 min, 120 min, 240 min and 360 min. |
| Secondary outcome measures | 1. Cmax of total thyroxin in the serum during a 6-hour period after ingestion of levothyroxine 2. Tmax of total thyroxin in the serum during a 6-hour period after ingestion of levothyroxine |
| Overall study start date | 15/03/2023 |
| Overall study end date | 31/12/2024 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 65 Years |
| Sex | Both |
| Target number of participants | 12 |
| Participant inclusion criteria | 1. Age 18-65 years 2. Informed Consent as documented by signature |
| Participant exclusion criteria | 1. Contraindications to the drugs under study, e.g. known hypersensitivity or allergy 2. Need for any kind of drug therapy for the duration of the study 3. Women who are pregnant or breastfeeding 4. Intention to become pregnant during the course of the study 5. Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration. Female participants who are surgically sterilised / hysterectomized or post-menopausal for longer than 2 years are not considered as being of child bearing potential. 6. Other clinically significant concomitant disease states (e.g., renal failure, thyroid dysfunction, cardiovascular disease, arterial hypertension, any other medical condition that could lead to an albumin deficiency such as anorexia etc.) 7. Abnormal findings in the screening tests (laboratory, ECG, physical examination). 8. Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant 9. Participation in another study with investigational drug within the 30 days preceding and during the present study 10. Previous enrolment into the current study 11. Enrolment of the investigator, his/her family members, employees and other dependent persons |
| Recruitment start date | 01/12/2023 |
| Recruitment end date | 30/06/2024 |
Locations
Countries of recruitment
- Switzerland
Study participating centre
Rämistrasse 100
Zürich
8091
Switzerland
Sponsor information
Hospital/treatment centre
Rämistrasse 100
Zurich
8091
Switzerland
| Phone | +41 (0)442554074 |
|---|---|
| jerome.bonzon@usz.ch | |
| Website | http://www.en.usz.ch/Pages/default.aspx |
"ROR" |
https://ror.org/01462r250 |
Funders
Funder type
University/education
Government organisation / Universities (academic only)
- Alternative name(s)
- University of Zurich, Switzerland, University of Zurich, UZH
- Location
- Switzerland
Results and Publications
| Intention to publish date | 31/12/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. |
| IPD sharing plan | The datasets generated and/or analysed during the current study will be published as a supplement to the results publication. |
Editorial Notes
17/10/2023: Trial's existence confirmed by Kantonale Ethikkommission Zürich.
