Fig. 1

SPIRIT Study diagram. W n : week number, D: daily W: weekly. The study duration is 18 weeks. After the baseline assessment at time 0, patients will have two pairs of active drug (3 weeks) and placebo (3 weeks) exposures. Randomly assigned treatment pairs will comprise two treatment periods (active therapy or placebo) separated by a 2-week washout period. Treatment pairs will also be separated by washout periods