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

NCT02245165 | Completed Phase 1

• 1 other identifier: LNMMA-UU-02
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastrointestinal Motility Disorder; Disturbance of Salivary Secretion

Keywords

Nitric oxide; Nitric oxide synthase; Gastrointestinal motility; Gut peptide hormones

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Reduced exhaled NO after administration of NO synthase inhibitor LNMMA

  1 year

Study Arms (2)

Nitric oxide synthase (NOS) inhibition

EXPERIMENTAL

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

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

Saline

SHAM COMPARATOR

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

Biological: saline

Interventions

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

Also known as: L-NMMA

Nitric oxide synthase (NOS) inhibition

saline BIOLOGICAL

Saline

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers 18-50 years of age

You may not qualify if:

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

Sponsors & Collaborators

• Uppsala University: lead
• Bengt Ihre Foundation: collaborator
• The Swedish Society of Medicine: collaborator

Study Sites (1)

Uppsala University

Uppsala, Uppsala County, 75185, Sweden

Location

MeSH Terms

Interventions

omega-N-Methylarginine; Sodium Chloride

Intervention Hierarchy (Ancestors)

Arginine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Per M Hellstrom, MD, prof

  Uppsala University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2014
• First Posted: September 19, 2014
• Study Start: June 1, 2013
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: September 19, 2014

Record last verified: 2014-09

Locations

SE (1)