Drug interaction study with thyroid hormone and zinc preparation in healthy volunteers
| ISRCTN | ISRCTN73459064 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN73459064 |
| Secondary identifying numbers | 1.2 |
- Submission date
- 14/08/2024
- Registration date
- 14/08/2024
- Last edited
- 14/08/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- 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, there is no information about how zinc, which is also a similar kind of mineral, affects the absorption of levothyroxine. Zinc might also have an impact on how your body takes in levothyroxine. So, this study aims to figure out how much zinc affects the absorption of levothyroxine.
Who can participate?
Healthy volunteers aged 18-65 years old 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 whether participants can participate in the study. If participants meet all the requirements to join the study, they will be randomly assigned to one of three groups: one that takes levothyroxine by itself, one that takes levothyroxine with 10 mg zinc, and one that takes levothyroxine with 50 mg zinc. During each of these administrations, thyroxine levels will be measured at a total of 6 different time points. This helps to calculate and compare the area under the curve (AUC) for thyroxine. To make the process more comfortable and avoid the need for multiple needle pricks during each visit, blood will be drawn using a catheter in a vein. 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 6 months, 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 and the high dose of zinc, 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 the standard dose of zinc (10 mg) is not likely to pose a significant risk to subjects, and also for the slightly higher dose (50 mg) the potential adverse events of soft stool/diarrhea or headache are 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?
May 2024 to December 2025
Who is funding the study?
University of Zurich (Switzerland). This is an investigator-initiated clinical trial and thus has no external sponsoring.
Who is the main contact?
Dr Jérôme Bonzon, jerome.bonzon@usz.ch
Contact information
Public, Scientific, Principal Investigator
Department of Clinical Pharmacology and Toxicology
Rämistrasse 100
Zürich
8091
Switzerland
| Phone | +41 44 255 40 74 |
|---|---|
| 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, Telephone |
| Study type | Safety |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | Single centre drug-drug interaction study with levothyroxine and zinc-D-gluconate in healthy subjects |
| Study acronym | ThyroZinc |
| Study hypothesis | The treatments with a zinc compound in two different dosages will dose-dependently reduce the AUC of thyroxine manner compared to levothyroxine alone. The null hypothesis is that the three treatments do not differ regarding the AUC of thyroxine. |
| Ethics approval(s) |
Approved 26/07/2024, Cantonal Ethics Committee Zurich (Kantonale Ethikkommission Zürich) (Stampfenbachstrasse 121, Zürich, 8090, Switzerland; +41 43 259 79 70; admin.kek@kek.zh.ch), ref: 2024-01028 |
| Condition | Hypothyroidism |
| Intervention | This is a cross-over study with three groups. Each of the three treatments will last for 360 minutes, which is the duration needed for blood sample collection. A washout period of at least 4 weeks will be scheduled between each treatment. No additional follow-up is planned for the study. Group 1: One dose of zinc-D-gluconate (70 mg, corresponding to 10 mg zinc) in tablet form, taken orally along with levothyroxine 1 mg Group 2: One dose of zinc-D-gluconate (350 mg, corresponding to 50 mg zinc) in tablet 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 + zinc 10 mg and C being levothyroxine + zinc 50 mg. 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 who is not involved in the trial. Only after sealing will the envelopes be handed to the investigators. After the 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 16th participant who replaces the participant who did not complete all visits). |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic, Bioequivalence |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Euthyrox® (Levothyroxin-Natrium), Zink Biomed® 10 |
| Primary outcome measure | AUC of total thyroxin in the serum up to 6 hours after ingestion of levothyroxine measured using electrochemiluminescence immunoassay (ECLIA) at 0, 30, 60, 120, 240 and 360 min |
| Secondary outcome measures | 1. Cmax of total thyroxin in the serum measured using electrochemiluminescence immunoassay (ECLIA) during a 6-hour period after ingestion of levothyroxine 2. Tmax of total thyroxin in the serum measured using electrochemiluminescence immunoassay (ECLIA) during a 6-hour period after ingestion of levothyroxine |
| Overall study start date | 17/05/2024 |
| Overall study end date | 31/12/2025 |
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 | 15 |
| Participant inclusion criteria | 1. Age 18-65 years old 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 oral drug therapy (including oral contraceptive or nutritional supplements) for the duration of the study, except for the symptomatic treatment of common conditions like headache, musculoskeletal pain, common cold, gastritis, nausea and diarrhoea with medication containing paracetamol, non-steroidal anti-inflammatory drugs, meclizine, domperidone, and loperamide, as long they are taken on an as-per-need basis and not 72 hours before a visit. 3. Planned intake of oral calcium, magnesium, zinc or iron supplements for the duration of the study 4. 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.) 5. Abnormal findings in the screening tests (laboratory, ECG, physical examination). 6. Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant 7. Participation in another study with an investigational drug within the 30 days preceding and during the present study 8. Previous enrolment into the current study 9. Enrolment of the investigator, his/her family members, employees and other dependent persons Applicable only to female participants: 1. Women who are pregnant or breastfeeding 2. Intention to become pregnant during the study 3. 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 (defined as sexual abstinence with men (except in case of medically proven male sterility of the male sexual partner), use of a condom, use of an intrauterine device (contraceptive coil with or without hormones), use of a dermal or subcutaneous device or a subcutaneous injection with hormones (such as Evra® or Implanon®), use of a vaginal hormonal device (such as NuvaRing®)) 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 childbearing potential. |
| Recruitment start date | 26/07/2024 |
| Recruitment end date | 31/12/2024 |
Locations
Countries of recruitment
- Switzerland
Study participating centre
Rämistrasse 100
Zürich
8091
Switzerland
Sponsor information
Hospital/treatment centre
Department of Clinical Pharmacology and Toxicology, Rämistrasse 100
Zürich
CH-8091
Switzerland
| Phone | +41 44 255 20 68 |
|---|---|
| pharmakologie@usz.ch | |
| Website | https://www.usz.ch/ |
"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 | 31/12/2026 |
|---|---|
| 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 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
14/08/2024: Study's existence confirmed by the Cantonal Ethics Committee Zurich.
