Objective and subjective results of a randomized, double-blind, placebo-controlled trial using cisapride to treat gastroparesis

Abstract

Cisapride, a relatively new gastrointestinal prokinetic agent, has been reported to increase gastric emptying and improve symptoms of gastroparesis. We investigated these effects of cisapride in patients with severe idiopathic and diabetic gastroparesis during an eight-week trial. The study design was a two-week single-blind placebo run in period to exclude placebo responders, followed by a six-week randomized, double-blind, placebo-controlled treatment phase. Delayed gastric emptying of solids on radionuclide scan and a minimum symptom intensity score were inclusion criteria. Forty-three patients were entered: four placebo responders and one other patient were excluded, leaving 19 patients randomized to cisapride (20 mg per os three times a day before meals), and 19 patients to placebo. Seven individual symptoms of gastroparesis were scored in a daily diary and reviewed at two-week visits. Sixteen patients in the cisapride group were able to complete the trial compared to 12 on placebo. The gastric emptying study was repeated at the end of treatment or at the time of withdrawal for those who dropped out. Cisapride significantly increased solid gastric emptying relative to baseline (P = 0.005) whereas placebo did not (P > 0.10). Cisapride did not significantly improve any symptom of gastroparesis relative to baseline or to placebo. We conclude that in a population of severe, refractory gastroparetic patients cisapride significantly accelerates gastric emptying of a solid meal without significantly reducing symptoms during a short-term treatment trial compared to placebo. Further trials of cisapride in less advanced and "end-stage" gastroparetics than studied here or combining cisapride with other prokinetic agents or antiemetics, are warranted.

Prokinetics in Patients with Gastroparesis: A Systematic Analysis

“…The majority of the studies included patients with diabetic gastroparesis [9, 12, 13, 16, 24, 26, 27, 28, 29, 30, 31, 32, 33, 35, 36, 37, 38, 39], patients with diabetic and idiopathic gastroparesis [8, 10, 15, 17, 18, 20, 21, 23]or patients with only idiopathic gastroparesis [22, 25]. Two of the studies also included patients with gastroparesis due to a collagenosis [11, 34]; 2 papers did not provide information regarding the underlying etiology [14, 19].…”

“…In 23 of the 32 studies, the gastric emptying times were measured ( 99m Tc) for solids only [8, 9, 10, 13, 14, 16, 17, 18, 20, 21, 22, 23, 24, 25, 27, 29, 30, 31, 34, 35, 36, 38, 39], while 8 studies assessed the emptying of solid and liquid compounds [11, 12, 15, 19, 28, 32, 33, 37]. One study measured liquids only [26].…”

“…Four studies using clonidine, renzapride, EM523L and levosulpiride were excluded because only one trial was done with each of these compounds, resulting in a patient number that was too low to achieve statistical significance [4, 5, 6, 7]. This left 32 studies involving a total of 496 patients eligible for further analysis [8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39]. Four of these 32 studies measured the influence of two different prokinetic agents on gastric emptying and symptom score and, because of this, were analyzed separately for each drug [14, 16, 20, 31].…”

Gastroparesias: revisão de aspectos relacionados ao conceito, à etiopatogenia e ao manejo clínico

“…Entre os pontos que merecem menção, destacam-se a dissociação encontrada em alguns trabalhos entre efeito sobre os sintomas e ação restauradora do esvaziamento gástrico. Em alguns estudos, verificou-se correção inequívoca do retarde do esvaziamento gástrico, mas ausência de efeito sobre os sintomas 23 . Outra limitação ao uso das drogas pró-cinéticas é a tendência, quase uniforme, de haver perda do efeito terapêutico com o passar do tempo 19,24 .…”

Relationship between the Effects of Cisapride on Gastric Emptying and Plasma Glucose Concentrations in Diabetic Gastroparesis

“…Cisapride stimulates gastro-intestinal motility by facilitating acetylcholine release from the myenteric plexus via a 5-HT 4 receptor mechanism [31]. A number of studies have evaluated the effects of cisapride on gastric emptying in diabetic gastroparesis [32, 33, 34, 35, 36, 37, 38, 39, 40, 41]. While in the majority of these studies cisapride has been shown to accelerate gastric emptying, in others the results were equivocal or negative [37, 38, 41].…”