A Novel, Duodenal-Release Formulation of a Combination of Caraway Oil and L-Menthol for the Treatment of Functional Dyspepsia: A Randomized Controlled Trial

Abstract

Objectives: We conducted a randomized, placebo-controlled trial, which evaluated a novel formulation of caraway oil and L-menthol using microsphere-based site-specific targeting (COLM-SST) vs placebo in patients with functional dyspepsia (FD).

Methods: Adult men and women with FD defined by Rome III criteria were recruited. Patients were randomized to COLM-SST (25 mg of caraway oil and 20.75 mg of L-menthol per capsule, at 2 capsules per dose, twice per day) or placebo. Efficacy was measured at 24 hours, 2 weeks, and 4 weeks. Patients were allowed to take concomitant medications for their FD throughout the trial, and rescue medicines were allowed, 48 hours after start of dosing.

Results: Ninety-five patients were enrolled (mean age = 43.4 years; 75.8% women). At 24 hours, the active arm reported a statistically significant reduction in postprandial distress syndrome symptoms (P = 0.039), and a nonsignificant trend toward benefit of epigastric pain syndrome symptoms (P = 0.074). In patients with more severe symptoms, approximately 3 quarters of patients showed substantial global improvement (i.e., clinical global impressions), after 4 weeks of treatment, vs half in the control arm. These differences were statistically significant for patients with epigastric pain syndrome (P = 0.046), and trending toward significance for patients with postprandial distress syndrome (P = 0.091). There was no statistically significant difference between groups for Global Overall Symptom scores for the overall population at 2 and 4 weeks. Treatment emergent adverse events were mild to moderate, and no serious adverse events were reported.

Discussion: In patients taking their usual medications for FD, COLM-SST provided rapid relief (within 24 hours) and relief of severe FD symptoms. It was safe and well tolerated.

Figure 1.

FDREST consort chart. COLM-SST, caraway oil and L-menthol using microsphere-based Site-Specific Targeting; FDREST, Functional Dyspepsia Reduction Evaluation and Safety Trial; H2RA, histamine type-2 receptor antagonist; PPI, proton pump inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant.

Figure 2.

Response to COLM-SST in the intent to treat (ITT) population–change in GOS scores at the 24-hour time point (a) CGI at day 28 (b). COLM-SST, caraway oil and L-menthol using microsphere-based Site-Specific Targeting; CGI, clinical global impression; EPS, epigastric pain syndrome; GOS, Global Overall Symptom; PDS, postprandial distress syndrome.

Figure 3.

Response to COLM-SST in the PDS subgroup of ITT population (COLM-SST n = 18, control n = 16)—change in GOS scores at the 24-hour time point (a) change in CGI at day 28 (b). COLM-SST, caraway oil and L-menthol using microsphere-based Site-Specific Targeting; CGI, clinical global impression; EPS, epigastric pain syndrome; GOS, Global Overall Symptom; PDS, postprandial distress syndrome.

Figure 4.

Response to COLM-SST in the EPS subgroup of ITT population (COLM-SST n = 19, control n = 20)—change in GOS scores at the 24-hour time point (a) change in CGI at day 28 (b). COLM-SST, caraway oil and L-menthol using microsphere-based Site-Specific Targeting; CGI, clinical global impression; EPS, epigastric pain syndrome; GOS, Global Overall Symptom; PDS, postprandial distress syndrome.