Tegaserod in patients with mechanical sensitivity and overlapping symptoms of functional heartburn and functional dyspepsia

ABSTRACT

Background: While functional heartburn (FH) and functional dyspepsia (FD) are recognized clinical entities, symptoms often overlap across both disorders. Despite their frequency, little is known of the underlying pathophysiology of overlapping symptoms. This study evaluated the effect of the 5-HT₄ agonist, tegaserod, on visceral sensitivity and symptom improvement in patients with overlapping symptoms of FH and FD.

Research design and methods: Patients with overlapping symptoms of FH and FD (ROME II) and mechanical hypersensitivity (Barostat examination) were randomized to tegaserod 6 mg bid or placebo for 2 weeks with treatment crossover after a 2-week washout period. Esophageal and gastric Barostat sensory tests were performed and patients rated their overall symptoms at study end. When carry-over was detected, data were presented for period 1 only. Safety was also assessed.

Results: Sixty patients were screened of whom 30 were randomized and 25 completed. Mechanical hypersensitivity was reported by 83% of 47 patients completing esophageal and gastric baseline Barostat examinations. Tegaserod did not significantly alter balloon volume to pain (primary variable); however, pressure to gastric pain increased (p = 0.044 vs. placebo). The severity of heartburn, regurgitation, early fullness, and bloating was significantly lower following tegaserod vs. placebo treatment (p = 0.026, p = 0.021, p = 0.016, and p = 0.030). Overall symptom improvement was reported by 52% tegaserod vs. 32% placebo patients (p = 0.275), and treatment was well tolerated.

Conclusions: Results suggest that tegaserod may increase the gastric pain threshold and decrease the severity of individual symptoms in patients with overlapping FH and FD. However, these findings must be considered within the context of the study limitations, including the small number of subjects, potential for and presence of a carry-over effect, along with the impact of Barostat balloon use on the assessment of gastric function.

Key words: :

• Functional dyspepsia
• Functional heartburn
• Gastrointestinal
• Mechanical hypersensitivity
• Tegaserod

Acknowledgments

Declaration of interest: This study was supported by a grant from Novartis Pharmaceuticals, East Hanover, New Jersey. The authors acknowledge the contribution and editorial support provided by Dr Nicci Crofts of ACUMED® in the preparation of this manuscript. ACUMED's contribution was funded by Novartis. SR-S now works for Takeda Pharmaceuticals North America Inc., IL, USA. PBM is a Speaker and Consultant to Novartis. HMP has served as a Consultant to Novartis and the Oklahoma Foundation for Digestive Research. FK is employed as Senior Associate Director of Biostatistics at Novartis. IB is employed as a Medical Director at Novartis. Clinicaltrials.gov registration number: NCT00171457.