Assessing penetration of high dose Nicotinamide (Vitamin B3) in synovial fluid

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 Treg next to suppressing activation of
Teff and thereby restoring this balance is therefore a promising novel
therapeutic strategy. Current treatment, like DMARDS and biologicals, however
focuses primarily on influencingTeff. 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, most
recent research shows that, next to the effect on Treg, nicotinamide showed to
have an inhibitory effect on Tcell proliferation and activation. Treatment with
nicotinamide 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. This
trial aims to be a first step in the preparation of a large phase III clinical
trial to elucidate on the potential role of Vitamin B3 in the treatment of JIA.

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
bioavailability of NAM in patients with JIA at the side of inflammation, and
therefore it*s potential as a therapeutic agent, is yet unknown. The primary
objective of this study is therefore to assess the penetration of orally
ingested NAM in the synovial fluid.

open label, phase II study

Additional NAM therapy with 1,8g/m2/day in 3 doses for the duration of 3 days
before intra-articular corticosteroid injection.

Due to the study design the burden of participation of this study is considered
minimal due to a very short duration of treatment and by combining blood
sampling with blood sampling for routine clinical care, with the exception of 1
capillary blood sampling. No serious adverse events are expected since the very
short duration of treatment and the extensive previous experience with use of
high dose NAM in clinical trials in both children and adults for extensive
periods. Due to the short duration of treatment It is not expected that
participation is beneficial to the patients.