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

Gastrointestinal Motility Disorder Clinical Trial

— LNMMA  

Official title:

Nitric Oxide Control of the Migrating Motor Complex in Man: L-NMMA Effects in Relation to Muscarinic and Serotonergic Receptor Blockade

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02245165
• Other study ID #: LNMMA-UU-02
• Secondary ID: LNMMA-UU-02
• Status: Completed
• Phase: Phase 1
• First received: May 5, 2014
• Last updated: September 16, 2014
• Start date: June 2013
• Est. completion date: May 2014

Study information

• Verified date: September 2014
• Source: Uppsala University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Swedish Research Council
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Healthy volunteers 18-50 years of age

Exclusion Criteria:

• Age < 18, or > 50 years

• Any disease

• Any medication

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Disturbance of Salivary Secretion
• Gastrointestinal Motility Disorder

Intervention

Biological:
• L-Nitro-Monomethyl-Arginine (LNMMA) 10 mg/kg IV

• saline

Locations

Country	Name	City	State
Sweden	Uppsala University	Uppsala	Uppsala county

Sponsors (3)

Lead Sponsor	Collaborator
Uppsala University	Bengt Ihre Foundation, The Swedish Society of Medicine

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect on phases I-III of the migrating motor complex	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.	1 year	No
Secondary	Reduced exhaled NO after administration of NO synthase inhibitor LNMMA	After administration of a Nitric oxide synthase (NOS) inhibitor exhaled NO is used as a marker of reduced NOS activity.	1 year	No