Overview
Sponsor-declared trial summary
Rheumatoid Arthritis
The main objective of this study is to investigate the efficacy of 4 weeks of high dose oral thiamine as treatment for chronic fatigue in patients with rheumatoid arthritis. The primary outcome is a change in fatigue level immediately after 4 weeks of treatment, measured using the Bristol Rheumatoid Arthritis Fatigue M…
Key facts
- Sponsor
- Aarhus University Hospital
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Immune System Diseases [C20]
- Trial duration
- 16 Feb 2023 → 30 Aug 2023
- Decision date (initial)
- 2022-10-20
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Gigtforeningen, Denmark
External identifiers
- EU CT number
- 2022-500922-13-00
- WHO UTN
- U1111-1279-1416
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
The main objective of this study is to investigate the efficacy of 4 weeks of high dose oral thiamine as treatment for chronic fatigue in patients with rheumatoid arthritis. The primary outcome is a change in fatigue level immediately after 4 weeks of treatment, measured using the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ).
Secondary objectives 3
- To investigate the patients’ quality of life during the study period.
- To investigate the association between fatigue levels, thiamine levels and lactate concentration in the blood.
- To investigate possible side effects to the treatment.
Conditions and MedDRA coding
Rheumatoid Arthritis
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | PT | 10039073 | Rheumatoid arthritis | 100000004859 |
| 21.0 | LLT | 10062719 | Seronegative rheumatoid arthritis | 10028395 |
| 21.0 | LLT | 10040107 | Seropositive rheumatoid arthritis | 10028395 |
| 21.1 | LLT | 10003268 | Arthritis rheumatoid | 10028395 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Rheumatoid arthritis diagnosed > 3 months ago.
- In remission/mild disease activity (CRP < 10 mg/l, MD-HAQ < 1,3, DAS28 < 3,2)
- Chronic fatigue (duration of fatigue ≥ 6 months, BRAF total fatigue score ≥ 16)
- Age ≥18 years
- Signed informed consent
- Anticontraceptive (People who can get pregnant will need to use a safe anticontraceptive during the trial (12 weeks). Safe anticontraceptive is defined as: combination pills, intrauterine device, depot injection, subdermal implant, hormonal vaginal ring, or transdermal depot patch)
Exclusion criteria 3
- Patients with co-morbidity which can explain the participants fatigue, including: Anaemia (haemoglobin < 7,1 mmol/l [female]; < 8,1 mmol/l [male], Iron deficiency (Ferritin < 30 μg/l), Vitamin B12 deficiency (Vitamin B12 <125 pmol/l), Folate deficiency (Folate < 9 nmol/l), Vitamin D deficiency (25-Hydroxy-Vitamin D[D3+D2] < 50 nmol/l), Diabetes (HbA1c ≥ 48 mmol/mol or medication), Hypo/hyperthyroidism (TSH <0,300 or > 4,5 IU/l or medication)
- Participants who are unable to cooperate and follow the protocol
- Pregnant patients
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- A change in fatigue level immediately after 4 weeks of high-dose thiamine treatment. The minimal clinically important difference (MCID) is a decrease of 7,43 points or an increase of 2,58 points on the BRAF-MDQ total fatigue score.
Secondary endpoints 3
- A change in the patients’ quality of life at week 4, 8 and 12. Difference in EQ-5D score, MCID of 0,04.
- A change in blood lactate concentration at week 4, 8 and 12.
- Side effects to the treatment.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SCP38805888 · ATC
- Active substance
- Benfotiamine
- Route of administration
- ORAL
- Max daily dose
- 1800 mg milligram(s)
- Max total dose
- 50400 mg milligram(s)
- Max treatment duration
- 28 Day(s)
- Authorisation status
- Authorised
- ATC code
- A11DA01 — THIAMINE (VIT B1)
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Aarhus University Hospital
- Sponsor organisation
- Aarhus University Hospital
- Address
- Palle Juul-Jensens Boulevard 99
- City
- Aarhus N
- Postcode
- 8200
- Country
- Denmark
Scientific contact point
- Organisation
- Aarhus University Hospital
- Contact name
- Department of Rheumatology, AUH
Public contact point
- Organisation
- Aarhus University Hospital
- Contact name
- Department of Rheumatology, AUH
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Ended | 40 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Denmark | 2023-02-16 | 2023-08-30 | 2023-02-16 | 2023-05-26 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| Summary of Results TACRAF SUM-42988
|
2024-08-28T11:37:00 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| Summary of Results for laypersons TACRAF | 2024-08-28T11:37:08 | Submitted | Laypersons Summary of Results |
Documents 2 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | Summary of results for laypersons | 1.0 |
| Summary of results (for publication) | Summary of Results | 1.0 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2022-08-15 | Denmark | Acceptable 2022-10-20
|
2022-10-20 |
| 2 | SUBSTANTIAL MODIFICATION | SM-4 | 2022-12-14 | Denmark | Acceptable 2023-01-27
|
2023-01-27 |
| 3 | SUBSTANTIAL MODIFICATION | SM-5 | 2023-02-17 | Denmark | Acceptable 2023-03-03
|
2023-03-03 |