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

Uppsala University

Status and phase: Completed; Phase 1

Conditions: Disturbance of Salivary Secretion; Gastrointestinal Motility Disorder

Treatments: Biological: L-Nitro-Monomethyl-Arginine (LNMMA) 10 mg/kg IV; Biological: saline

Study type: Interventional

Funder types: Other

Identifiers

NCT02245165

LNMMA-UU-02 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 29 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy volunteers 18-50 years of age

Exclusion criteria

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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29 participants in 2 patient groups

Nitric oxide synthase (NOS) inhibition

Experimental group

Description:

After a control period of 4 hours, intervention with L-NMMA (10 mg/kg IV) is done and recording continued for 4 hours.

Treatment:

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

Saline

Sham Comparator group

Description:

After a control period of 4 hours, intervention with saline is done and recording continued for 4 hours.

Treatment:

Biological: saline