Colon transit (CT) measurements are used in the management of significant constipation. The radiopaque marker (ROM) method provides limited information. We proposed to validate wireless motility capsule (WMC), that measures pH, pressure and temperature, to ROM measurement of CT in patients with symptomatic constipation evaluated at multiple centers.Of 208 patients recruited, 158 eligible patients underwent simultaneous measurement of CT time (CTT) using ROM (Metcalf method, cut off for delay >67 h), and WMC (cutoff for delay >59 h). The study was designed to demonstrate substantial equivalence, defined as diagnostic agreement >65% for patients who had normal or delayed ROM transit. The 87% overall agreement (positive and negative) validates WMC relative to ROM in differentiating slow versus normal CT in a multicenter clinical study of constipation.

Cannabinoid receptors (CBR) are located on cholinergic neurons in the brain stem, stomach, and colon. CBR stimulation inhibits motility in rodents. Effects in humans are unclear. Dronabinol (DRO), a nonselective CBR agonist, inhibits colonic motility and sensation. The aim of this study was to compare effects of DRO and placebo (PLA) on colonic motility and sensation in healthy volunteers. Fifty-two volunteers were randomly assigned (double-blind) to a single dose of 7.5 mg DRO or PLA postoperative with concealed allocation. A balloon-manometric assembly placed into the descending colon allowed assessment of colonic compliance, motility, tone, and sensation before and 1 h after oral ingestion of medication, and during fasting, and for 1 h after 1,000-kcal meal. There was an overall significant increase in colonic compliance (P = 0.045), a borderline effect of relaxation in fasting colonic tone (P = 0.096), inhibition of postprandial colonic tone (P = 0.048), and inhibition of fasting and postprandial phasic pressure (P = 0.008 and 0.030, respectively). While DRO did not significantly alter thresholds for first gas or pain sensation, there was an increase in sensory rating for pain during random phasic distensions at all pressures tested and in both genders (P = 0.024). In conclusion, in humans the nonselective CBR agonist, DRO, relaxes the colon and reduces postprandial colonic motility and tone. Increase in sensation ratings to distension in the presence of relaxation of the colon suggests central modulation of perception. The potential for CBR to modulate colonic motor function in diarrheal disease such as irritable bowel syndrome deserves further study.

Cannabinoid receptor (CBR) stimulation inhibits motility and increases food intake in rodents. Effects of CBR stimulation in human gastrointestinal (GI) tract are unclear. We compared effects of dronabinol (DRO) and placebo (PLA) on GI transit, gastric volume and satiation in humans. In a double-blind, randomized study, 30 healthy volunteers were randomly assigned to DRO 5 mg b.i.d. or PLA for three doses. We measured GI functions noninvasively: day 0, Ensure satiation test to measure maximum tolerated volume (MTV) and 30-min post-Ensure symptoms; day 1, scintigraphic transit ((111)In-egg meal) and fasting and postprandial gastric volume ((99Tcm)-SPECT); day 2, 24-h colonic transit and repeat satiation test. ancova was used to compare treatment groups with gender, age, and, for the satiation test, the baseline MTV, as covariates. A log-rank test was used to assess treatment effects on gastric emptying. Planned sample size had 80% power to detect 25-30% differences in primary end points. There was an overall retardation of gastric emptying with DRO (P = 0.018); this was more pronounced in females (P = 0.011), than in males (P = 0.184). No significant treatment differences were detected for gastric volumes, MTV, post-Ensure(R) symptoms, small bowel and colonic transit. Fasting gastric volume was greater in males receiving DRO compared with PLA (238 +/- 17 vs 185 +/- 16, P = 0.04). DRO retards gastric emptying in humans; effects are gender-related. Dronabinol also increases fasting gastric volumes in males.

TZP-102 for 28 days, at doses of 10-40 mg once daily, was well-tolerated and resulted in a reduction in symptoms of gastroparesis. The lack of correlation between symptom improvement and gastric emptying change is consistent with previous studies in diabetic gastroparesis, and emphasizes the value of patient-defined outcomes in determining therapeutic benefit.

Females are disproportionately affected by constipation, which is often aggravated during pregnancy. Bowel function also changes during the luteal phase of the menstrual cycle. The aim was to compare the effects of acute administration of female sex steroids on gastric emptying, small bowel transit and colonic transit in healthy postmenopausal subjects. A second aim was to determine whether withdrawal of the hormones was associated with a change in transit. Forty-nine postmenopausal females were randomized to receive for 7 days 400 mg day(-1) micronized progesterone, 0.2 mg day(-1) oestradiol, combination of the two, or placebo. Treatment groups were balanced on age. Participants underwent whole gut transit measurement by scintigraphy using a 99m-labeled technetium-egg meal and 111-labeled indium-charcoal via a delayed-release capsule. Transit measurement was repeated after withdrawal of the study medications. The primary endpoints were ascending colon (AC) emptying half-life time (t1/2) and colonic geometric centre (GC) at 24 h. Secondary analysis variables were GC at 4 and 48 h, gastric emptying t1/2 and colonic filling at 6 h. There was a significant overall effect of progesterone on colonic transit with shorter AC emptying t1/2 and significantly greater colonic GC at 48 h. No transit endpoints were altered by oestradiol or combined hormonal treatment relative to placebo. Oestradiol and progesterone resulted in looser stool consistency. Withdrawal of the hormone supplement was not associated with significant alteration in transit. Micronized progesterone does not retard colonic transit in postmenopausal females.