NAM, well known as a dietary supplement, has also been extensively studied in humans in a variety of diseases in both children and adults. However, the safety, tolerability of NAM in children with JIA is yet unknown. Furthermore, studies performed…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
In this phase II trial essential information will be gained on safety,
feasibility and tolerability of NAM as an additional treatment in JIA patients.
Secondary outcome
Additionally, PK/PD data will we obtained which can be used to develop an
optimal dosing scheme for a future phase III clinical trial. Next, preliminary
data on the effect of NAM on the function of regulatory T cells will be
acquired.
Background summary
In Juvenile Idiopathic Arthritis (JIA) there is a distortion in immunological
balance between regulatory T cells (Treg) and effector T cells (Teff).
Enhancing the suppressive function of regulatory T cells and thereby restoring
this balance is therefore a promising novel therapeutic strategy. Current
treatment, like DMARDS and biologicals, however focuses primarily on
influencing effector T cells. Interestingly, in the past few years it was found
that Vitamin B3, also known as nicotinamide (NAM) stabilizes FOXP3 expression
via inhibition of the histone deacetylase SIRT1. Through this mechanism it has
the potential to beneficially affect this immunological balance by positively
influencing regulatory T cell function. In addition to the effect on regulatory
T cells, NAM showed to have a down regulating effect on CD4+ and CD8+ cells and
could therefore influence both sides of the equation. We envision that NAM
maintenance treatment, when combined with established immunosuppressive
treatment, could help restore the immunological balance and hereby contribute
to gaining and maintaining remission in JIA patients.
Study objective
NAM, well known as a dietary supplement, has also been extensively studied in
humans in a variety of diseases in both children and adults. However, the
safety, tolerability of NAM in children with JIA is yet unknown. Furthermore,
studies performed on pharmacokinetics of NAM have only been performed in
adults. The primary objective of this study is therefore to assess safety,
feasibility and tolerability of NAM in de proposed dose in children with JIA.
Study design
An open label, phase II study will be performed.
Intervention
Additional NAM therapy with 1,2g/m2/day or 1,8g/m2/day in either 2 or 3 doses a
day during 3 months.
Study burden and risks
Due to the study design the burden of participation of this study has been
minimalized by combining clinical visits and blood sampling with routine
clinical care. Since JIA is a disease of childhood, this study can only be
performed in minors. No serious adverse events are expected since extensive
previous experience with use of high dose NAM in clinical trials in both
children and adults. Participation could be beneficial, since it is
hypothesized that additional NAM treatment could have a favourable effect on
the immunological balance in JIA and maintaining remission in these patients.
Lundlaan 6
Utrecht 3584EA
NL
Lundlaan 6
Utrecht 3584EA
NL
Listed location countries
Age
Inclusion criteria
- Patients with a diagnosis of oligo-articular or poly-articular JIA with active disease in 1 or multiple joints and an indication for intra-articular corticosteroid injection.
- Age between 4 to 18 years
- At the moment of inclusion, not on non-biological DMARD (Methotrexate) treatment or on stable DMARD treatment (at least 3 months of stable Methotrexate use).
Exclusion criteria
- no informed consent possible by patient/parents or caregivers
- participation in other interventional trials
- Treatment with biological DMARD
- Recently started treatment with non-biological DMARD (Methotrexate). Defined as treatment for a period less than 3 months.
- Use of systemic corticosteroids
- Relevant co morbidity: raised liver enzymes (>2x upper limit) and/or evidence of bone marrow failure (pancytopenia based upon full blood count).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-003643-10-NL |
| CCMO | NL61286.000.17 |
| Other | volgt nog |