pasireotide and Dumping-Syndrome

Dumping syndrome is a common and debilitating complication of upper gastrointestinal surgery. Accelerated gastric emptying and dysregulated secretion of gastrointestinal (GI) hormones are involved in its pathophysiology. Pasireotide, a novel somatostatin analogue, improved dumping in a phase-2 study. Preliminary data suggest that the glucagon-like peptide-1 (GLP-1) analogue liraglutide can also improve dumping. Short bowel syndrome is the most common cause of intestinal failure and involves not only a loss of mucosal absorptive area but also hypersecretion and accelerated transit. GLP-2 is the best studied hormone involved in intestinal adaptation. An increasing body of evidence demonstrates that the GLP-2 analogue teduglutide reduces parenteral support needs. New GLP-2 analogues and analogues of other GI hormones such as liraglutide are being investigated as promising treatments in short bowel syndrome.

Topics: Animals; Dumping Syndrome; Gastrointestinal Agents; Gastrointestinal Motility; Gastrointestinal Tract; Humans; Intestinal Absorption; Ligands; Liraglutide; Peptides; Receptors, Gastrointestinal Hormone; Short Bowel Syndrome; Signal Transduction; Somatostatin; Treatment Outcome

Dumping syndrome is a prevalent complication of oesophageal and gastric surgery characterised by early (postprandial tachycardia) and late (hypoglycaemia) postprandial symptoms.. To evaluate efficacy and safety of the somatostatin analogue, pasireotide in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery.. A single-arm, open-label, multicentre, intrapatient dose-escalation, phase 2 study with 4 phases: screening, 3-month SC (subcutaneous), 3-month IM (intramuscular) and 6-month optional extension IM phase. Primary endpoint was the proportion of patients without hypoglycaemia (plasma glucose <3.3 mmol/L [60 mg/dL] during an oral glucose tolerance test, OGTT) at the end of 3-month SC phase. A ≥50% response rate was considered clinically relevant.. Forty-three patients with late dumping were enrolled; 33 completed the 3-month SC phase and 23 completed the 12-month study. The proportion of patients without hypoglycaemia at month 3 (primary endpoint) was 60.5% (26 of 43; 95% confidence interval, 44.4%-75.0%). Improvement in quality of life was observed during SC phase, which was maintained in the IM phase. The proportion of patients with a rise in pulse rate of ≥10 beats/min during OGTT reduced from baseline (60.5%) to month 3 (18.6%) and month 12 (27.3%). Overall (month 0-12), the most frequent (>20% of patients) adverse events were headache (34.9%); diarrhoea, hypoglycaemia (27.9% each); fatigue, nausea (23.3% each); and abdominal pain (20.9%).. These results suggest that pasireotide is a promising option in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery.

Topics: Adult; Aged; Diarrhea; Dumping Syndrome; Female; Humans; Male; Middle Aged; Nausea; Quality of Life; Somatostatin

Dumping syndrome is characterized by distinct pathophysiological features such as postprandial increase in hematocrit (HT) and pulse rate (PR) and delayed hypoglycemia (HG). Treatment is based on dietary measures and somatostatin analogs (SA), but current SAs have incomplete efficacy, possibly through limited affinity for various somatostatin receptor subtypes. We evaluated the effect of pasireotide, a novel SA with high affinity for 4/5 human somatostatin receptors, on pathophysiological events and symptoms in dumping.. Randomized double-blind placebo-controlled cross-over study of nine patients (six women, 47 ± 4 years) with postoperative dumping. Baseline measurements included oral glucose tolerance testing (OGTT), abdominal ultrasound, and dumping symptom severity score (DSSS). Patients were treated for 2 weeks with placebo or pasireotide 300 μg s.c. t.i.d. with a 1-week wash-out in a randomized fashion. On day 13 and 14 of each treatment OGTT, DSSS, and solid and liquid gastric emptying (GE) were obtained.. Baseline OGTT was pathological in all patients based on PR (n = 5), HT (n = 1) or HG (n = 7). Compared to placebo, pasireotide suppressed the increase in PR (17.1 ± 2.8 vs 8.2 ± 3.5 bpm; p < 0.05) and late HG (nadir glycemia 55.6 ± 4.3 vs 83.3 ± 9.5 mg/dL; p = 0.007), increased peak glycemia (294.1 ± 33.3 vs 221.0 ± 23.1 mg/dL; p = 0.001) and delayed GE of solids (t1/2 83 ± 23 vs 43 ± 9 min; p = 0.05) and liquids (t1/2 70 ± 10 vs 40 ± 4 min, p = 0.05). The differences in DSSS did not reach statistical significance. Two patients dropped out because of adverse gastrointestinal events under pasireotide.. Pasireotide affects pathophysiological features of both early and late dumping syndrome.

Topics: Abdomen; Cross-Over Studies; Double-Blind Method; Dumping Syndrome; Female; Hormones; Humans; Male; Middle Aged; Pilot Projects; Placebos; Postoperative Complications; Severity of Illness Index; Somatostatin; Treatment Outcome