Trial of mycophenolate for persistent symptoms of hypothyroidism
| ISRCTN | ISRCTN68248063 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN68248063 |
| IRAS number | 1010665 |
| Secondary identifying numbers | 10785, CPMS 65473 |
- Submission date
- 16/05/2025
- Registration date
- 17/07/2025
- Last edited
- 11/08/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims
The TRIUMPH trial is investigating whether a drug called mycophenolate mofetil can help women aged 18 to 50 with an underactive thyroid who continue to experience symptoms such as tiredness, lethargy, weight issues, aches and pains and 'brain fog'. The study is exploring whether ongoing inflammation in the thyroid might be causing these symptoms and if mycophenolate mofetil can help reduce the inflammation and help patients feel better.
Who can participate?
Female patients with Hashimoto thyroiditis aged 18 - 50 years.
What does the study involve?
Participants will be randomly allocated to take either mycophenolate mofetil or placebo (a ‘dummy’ treatment) tablets. A total of 48 people will join the trial. Most will get the drug mycophenolate (30 people), and 18 will get a placebo (a dummy pill). You will take a tablet twice a day for four months. Neither you nor your doctors will know which treatment you are getting until the trial is finished.
What are the possible benefits and risks of participating?
Mycophenolate mofetil is used to treat many inflammatory and immune-related conditions like arthritis and autoimmune liver disease. It has not been used in people with Hashimoto’s Thyroiditis before, but it has been safely used for over 25 years.
Where is the study run from?
Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
May 2025 to April 2028
Who is funding the study?
Medical Research Council (UK)
Who is the main contact?
Triumph@newcastle.ac.uk
Contact information
Scientific, Principal Investigator
Translational and Clinical Research Institute, Newcastle University
Newcastle upon Tyne
NE2 4HH
United Kingdom
| Phone | +44 191 2418674 |
|---|---|
| simon.pearce@newcastle.ac.uk |
Public
Newcastle Clinical Trials Unit, Newcastle University, Baddiley Clark Building
Newcastle-upon-Tyne
NE2 4NQ
United Kingdom
| Phone | +44 191 208 0656 |
|---|---|
| triumph@newcastle.ac.uk |
Study information
| Study design | Interventional double blind randomized parallel group placebo controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Safety, Efficacy |
| Scientific title | Trial of Mycophenolate for Persistent symptoms of Hypothyroidism |
| Study acronym | TRIUMPH |
| Study objectives | Primary objective: Determine whether MMF treatment can reduce thyroid inflammation in patients with Hashimoto thyroiditis Secondary objectives: 1. Determine whether MMF treatment can ameliorate symptoms of hypothyroidism and improve wellbeing. 2. Determine whether changes in thyroid inflammation correlate with changes in symptoms and wellbeing. 3. Determine whether MMF treatment can reduce thyroid lymphocyte metabolic activity as judged by nuclide (FDG-PET) imaging in patients with Hashimoto thyroiditis. 4. Determine whether MMF treatment changes serum markers of inflammation in Hashimoto thyroiditis patients. 5. Determine whether MMF treatment is associated with change in other inflammatory cell populations (including CD4, CD8, CD19, CD56 positive lymphocytes) in Hashimoto’s thyroiditis patients. 6. Determine whether MMF treatment changes serum thyroid hormones. 7. Determine whether MMF treatment can change cognitive function. 8. Determine whether changes in serum inflammatory markers are associated with changes in symptoms and wellbeing. 9. Determine if MMF is safe in this patient group. 10. Consider the long-term effect of MMF on quality of life. |
| Ethics approval(s) |
Not yet submitted, To be confirmed, ref: 25/EM/0124 |
| Health condition(s) or problem(s) studied | Hashimoto's Thyroiditis |
| Intervention | Participants are randomised using an online system to receive either Mycophenolate Mofetil (MMF) tablets or matched placebo (“dummy” tablets). Participants will be randomised in a 5:3 ratio (30 participants to MMF and 18 to placebo). Participants will take a tablet orally twice daily, one in the morning and one in the evening. Participants will take trial treatment for 16 weeks and will be followed up until 22 weeks. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacodynamic, Therapy |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Mycophenolate mofetil Tillomed 500 mg film-coated tablets |
| Primary outcome measure | Change in numbers of CD45+ thyroid lymphocytes assayed by flow cytometry (baseline to 16 weeks) assayed from thyroid cellular aspirates |
| Secondary outcome measures | 1. Change in FACIT-F, ThyPRO39, SF-36, GHQ-12, and POMS2 scores (baseline to 8 and 16 weeks). 2. Correlation of changes in FACIT-F, ThyPRO39, SF-36, GHQ-12, and POMS2 scores with changes in the number of thyroid lymphocytes (baseline to 16 weeks). 3. Change in thyroid SUVmax during 18FDG-FDG PET/CT scanning (baseline to 16 weeks). 4. Change in serum TPOAb, TgAb, hsCRP, procalcitonin, ESR, and neutrophil-to-lymphocyte ratio (baseline to 8 and 16 weeks). 5. Change in numbers of CD4, CD8, CD19, and other thyroid lymphocyte subsets assayed by flow cytometry (baseline to 16 weeks). 6. Change in TSH, FT4, and FT3 (baseline to 8 and 16 weeks). 7. Change in cognitive function tests: digit-span, trail making, complex figure, and pinboard tests (baseline to 8 and 16 weeks). 8. Correlation of changes in FACIT-F, ThyPRO39, SF-36, GHQ-12, PSQI, POMS2, and WHO-5 scores with serum TPOAb, hsCRP, and other inflammatory markers (baseline to 16 weeks). 9. Change in serum liver function and blood count parameters (baseline to 8 and 16 weeks). 10. Adverse reactions up to 16 weeks. 11. Change in Levothyroxine dose. 12. Change in FACIT-F score at week 22. |
| Overall study start date | 12/05/2025 |
| Completion date | 30/04/2028 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 50 Years |
| Sex | Female |
| Target number of participants | 48 |
| Key inclusion criteria | 1. Female patients ≥18yrs and ≤50yrs old 2. Hashimoto thyroiditis with at least one documented serum TSH ≥7.0 mU/L 3. Current positive thyroid peroxidase antibodies (TPOAb ≥34 U/L) 4. Serum TSH currently within reference range 5. On stable dose of levothyroxine for at least 3 months 6. Persistent fatigue as judged FACIT-F score ≥7 and ≤35 7. For women of child-bearing potential (WOCBP), willing to use a highly effective contraceptive method during their participation in the trial 8. Able to understand and complete trial procedures (with translation or verbal explanation if required). 9. Willing and able to provide informed consent prior to any trial procedures taking place |
| Key exclusion criteria | 1. Previous thyroidectomy or radioiodine treatment 2. Pregnant or breastfeeding, or with a plan for pregnancy within 6 months; unwillingness to undergo regular pregnancy testing. 3. Hepatitis B & C or HIV infection 4. Anaemia (Hb ≤ 115g/l), thrombocytopenia (≤75 x10^9/L) or neutropenia (≤1.0 x10^9/L), abnormal ferritin, vitamin D (<50nmol/L), abnormal renal (creatinine ≥130umol/L) or liver function (ALT ≥50 U/L). 5. Obesity (BMI ≥30Kg/m²) 6. Co-existing autoimmune conditions excluding vitiligo, or positive for serum auto-antibodies suggestive of covert non-thyroidal autoimmunity 7. Any significant physical health condition that may explain persistent symptoms including cardiorespiratory disease, renal or hepatic failure, pancreatic disease, cancer (excluding non-melanoma skin cancer), nutritional deficiency, untreated chronic infection including TB 8. Previous hospitalisation due to psychosis, depression or anxiety, current HADS depression score >10 9. Consumes more than 20 units of alcohol per week 10. Current use of medication that would interfere with mycophenolate action, including proton pump inhibitors. 11. Current use of medication that precludes thyroid FNA including warfarin and DOACs 12. Current use of immunosuppressive therapy for other conditions (within 3 months) 13. Current or previous participation in a CTIMP or intervetional research study within 3 months 14. Hypersensitivity or anaphylactic reaction to mycophenolate mofetil or mycophenolic acid 15. Inability, in the opinion of the investigator, to be able to complete the clinical trial visits or procedures |
| Date of first enrolment | 30/03/2025 |
| Date of final enrolment | 30/11/2026 |
Locations
Countries of recruitment
- United Kingdom
Study participating centre
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
United Kingdom
Sponsor information
Hospital/treatment centre
Joint Research Office, Regent Point, Regent Farm Road
Newcastle upon Tyne
NE3 3HD
England
United Kingdom
| tnu-tr.sponsormanagement@nhs.net | |
| Website | http://www.newcastle-hospitals.org.uk/ |
"ROR" |
https://ror.org/05p40t847 |
Funders
Funder type
Research council
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/04/2029 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Peer reviewed scientific journals Internal report Conference presentation Publication on website Other publication Participants will give consent for the sharing of their anonymised trial data with other researchers, published in medical journals and at research meetings. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Triumph@newcastle.ac.uk |
Editorial Notes
11/08/2025: Internal review.
16/05/2025: Trial's existence confirmed by NHS HRA.
