Nitric Oxide Control of Migrating Motor Complex: L-NMMA Effects in Relation to Receptor Blockades

Phase 1

Completed

• Conditions: Gastrointestinal Motility Disorder; Disturbance of Salivary Secretion
• Interventions: Biological: L-Nitro-Monomethyl-Arginine (LNMMA) 10 mg/kg IV; Biological: saline

• Registration Number: NCT02245165
• Lead Sponsor: Uppsala University

Brief Summary

The aim is to elucidate how NO works in conjunction with other neurotransmitters to regulate the migrating motility complex (MMC). Twenty-two healthy volunteers should undergo water-perfused antroduodenojejunal manometry during a control period of 4 h, followed by another 4h after a bolus injection of either saline or the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 10 mg/kg intravenously) with or without atropine (1 mg) or ondansetron (8 mg). Effects on the MMC pattern are determined. Exhaled and rectal NO is monitored throughout the experiments. Effects of L-NMMA on the MMC pattern are analyzed against a background of atropine or ondansetron. Blood samples are drawn for analysis of simultaneous peptide hormone release into the bloodstream. Peptide hormone release will be correlated to the respective motility pattern elicited by LNMMA.

Detailed Description

Dysregulation of the cyclic motility pattern controlling propulsion during fasting, the migrating motor complex (MMC), can result in small intestinal bacterial overgrowth and symptoms of intestinal obstruction. Nitric oxide (NO) acts as an inhibitory neurotransmitter by relaxation of smooth muscle cells. Little is known on how NO works in conjunction with other neurotransmitters to regulate the MMC.

Methods: Twenty-two healthy volunteers (22-38 years) should undergo antroduodenojejunal manometry recordings for 8h, 4h of which as a control period with basal motility recording and 4h after a bolus injection of either saline or the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 10 mg/kg intravenously) with or without atropine (1 mg) or ondansetron (8 mg). The effects of L-NMMA on the MMC pattern are to be determined. Exhaled and rectal NO was monitored throughout the experiments as a means to secure efficient NO synthase inhibition.

Expected results: L-NMMA is expected to increase the intestinal motor activity, either as a direct effect on the small muscle cells, or through the release of some motility-stimulating gut peptide hormone (motility, ghrelin, somatostatin).

Expected conclusions: A NO donor, such as nitrite or nitrate which is converted to NO in an acidic milieu in the stomach may act as an inhibitor of motility. Thus, swallowed nitrite and nitrate from the saliva may contribute to the regulation of gastric emptying and gastrointestinal motility.

Study Timeline

• Study Start: 2013-06
• Primary Completion: 2014-05
• Study Completion: 2014-05
• Study First Submitted: 2014-05-05
• Status Verified: 2014-09
• Study First Submitted QC: 2014-09-16
• Last Update Submitted: 2014-09-16
• Study First Posted: 2014-09-19
• Last Update Posted: 2014-09-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

• Healthy volunteers 18-50 years of age

Exclusion Criteria

• Age < 18, or > 50 years
• Any disease
• Any medication

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nitric oxide synthase (NOS) inhibition	L-Nitro-Monomethyl-Arginine (LNMMA) 10 mg/kg IV	After a control period of 4 hours, intervention with L-NMMA (10 mg/kg IV) is done and recording continued for 4 hours.
Saline	saline	After a control period of 4 hours, intervention with saline is done and recording continued for 4 hours.

Primary Outcome Measures

Name	Time	Method
Effect on phases I-III of the migrating motor complex	1 year	NO is considered to be of importance for gastrointestinal motility. The MMC is measured as a biomarker of regulatory functions of gastrointestinal motility. Inhibition of the elaboration of NO by use of LNMMA is used to draw conclusions about the importance of NO for regulation of gastrointestinal motility.

Secondary Outcome Measures

Name	Time	Method
Reduced exhaled NO after administration of NO synthase inhibitor LNMMA	1 year	After administration of a Nitric oxide synthase (NOS) inhibitor exhaled NO is used as a marker of reduced NOS activity.

Trial Locations

Locations (1)

Uppsala University; 🇸🇪 Uppsala, Uppsala county, Sweden