DA-9701 for Gastrointestinal Symptoms in Postural Orthostatic Tachycardia Syndrome: A Randomized Pilot Study.

BACKGROUND/AIMS: : Patients with postural tachycardia syndrome (POTS) commonly experience gastrointestinal (GI) symptoms. We aim to assess the feasibility and preliminary efficacy data for DA-9701, a prokinetic agent targeting 5-hydroxytryptamine 1A, 5-hydroxytryptamine 4, and dopamine D2 receptors, in patients with POTS.

METHODS

: In a randomized, double-blind, placebo-controlled, single-center crossover trial, patients with POTS were given either 30 mg of DA-9701 or a placebo 3 times daily for eight weeks in a 1:1 ratio. After a 4-week washout, patients received the alternate treatment for another 8 weeks. The primary endpoint focused on assessing the change in GI symptoms (total Nepean Dyspepsia Index-Korean version [NDI-K] symptom score) from baseline over the 8 week-treatment period. Endpoints were assessed in all enrolled and randomized patients (intention-to-treat), and in those who completed the trial (per-protocol analysis).

RESULTS

: Between January 2022 and August 2023, 24 patients were randomized (n = 12 per group), with 3 discontinuing after randomization. DA-9701 did not significantly improve primary endpoints for total NDI-K symptom scores in either the intention-to-treat (least-squares means, -13.9 vs. -9.5, P = 0.326) or per-protocol analyses (-17.2 vs -12.0, P = 0.242). Notably, a trend toward improvement in specific GI symptoms, such as upper abdominal pain, was observed in both intention- to-treat (-0.6 vs 0.7; P = 0.066) and per-protocol analyses (-0.9 vs 0.6; P = 0.045). No serious adverse events were observed.

CONCLUSION

DA-9701 did not improve GI symptoms in this crossover trial; however, its potential effect on specific GI symptoms merits further investigation.