Clinical trial NCT02245165: Nitric Oxide Control of Migrating Motor Complex: L-NMMA Effects in Relation to Receptor Blockades
Official title: Nitric Oxide Control of the Migrating Motor Complex in Man: L-NMMA Effects in Relation to Muscarinic and Serotonergic Receptor Blockade
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gastrointestinal Motility Disorder
Disturbance of Salivary Secretion
Keywords: Nitric oxide
Nitric oxide synthase
Gastrointestinal motility
Gut peptide hormones
Lead sponsor: Uppsala University
Sponsor class: OTHER
Collaborators: name: Bengt Ihre Foundation
name: The Swedish Society of Medicine
First posted: 2014-09-19
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

* Healthy volunteers 18-50 years of age

Exclusion Criteria:

* Age \< 18, or \> 50 years
* Any disease
* Any medication

Primary outcomes:
measure: Effect on phases I-III of the migrating motor complex
timeFrame: 1 year
Secondary outcomes:
measure: Reduced exhaled NO after administration of NO synthase inhibitor LNMMA
timeFrame: 1 year
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Uppsala University
state: Uppsala county
Study officials:
affiliation: Uppsala University
name: Per M Hellstrom, MD, prof
role: PRINCIPAL_INVESTIGATOR
References: