NCT02820064

Brief Summary

Chronic Obstructive Pulmonary Disease (COPD) is characterized by chronic systemic hypoxia and low-grade inflammation as well as by an alteration of arginine (ARG) metabolism. As ARG is synthetized from circulating citrulline (CIT), an alteration of CIT homeostasis, particularly its production by ornithine transcarbamylase (OCT) in small intestine could be involved. We hypothesized that hypoxia +/- inflammation, classically associated to COPD, has effects on OCT regulation in enterocytes. This study aims at exploring the effects of hypoxia and inflammation on the production of citrulline by ornithine transcarbamylase (OTC) activity in enterocytes from explant cultures of duodenal tissue.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
30

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Jan 2016

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2016

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

June 28, 2016

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 30, 2016

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2017

Completed
Last Updated

December 6, 2016

Status Verified

December 1, 2016

Enrollment Period

1 year

First QC Date

June 28, 2016

Last Update Submit

December 5, 2016

Conditions

Outcome Measures

Primary Outcomes (1)

  • OCT activity in biopsy specimens

    OCT activity in duodenal biopsy specimens will be measured at the end of the incubation period and compared between the 4 different groups (standard/inflammatory/hypoxic:inflammatory+hypoxic conditions)

    OCT activity in biopsies after incubation

Study Arms (1)

only one arm

OTHER

Patients for who and esophagogastroduodenoscopy in order to diagnose is performed. 8 duodenal biopsy specimens will be removed.

Procedure: duodenal biopsy during gastroduodenal endoscopy

Interventions

Patients for who and esophagogastroduodenoscopy in order to diagnose is performed. 8 duodenal biopsy specimens will be removed.

only one arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Digestive disease known or suspected which justify an oeso-gastro-endoscopy with digestive biopsies, excepted a disease with duodenal localization known or strongly suspected.
  • Gastroscopy performed under general anaesthesia
  • Patient's written agreement obtained
  • Age \< 18
  • Therapeutical endoscopy (that is to say when a therapeutical act will be performed as balloon dilation, digestive or biliary prosthesis, drainage, diverticulotomy, polypectomy, variceal ligation...) either expected or
  • Duodenal pathology (known or strongly suspected with the clinical and biological elements)
  • Duodenal biopsies are not allowed to be performed: vascular lesions, digestive haemorrhage, clotting disorder.
  • Antiplatelet drug and anticoagulant drug
  • Lack of written agreement
  • Subjects hospitalized in an emergency state or without agreement
  • Subjects who cannot be contacted in emergency.

You may not qualify if:

  • subjects will be excluded from the study:
  • if an unexpected therapeutic act has to be performed during the endoscopy
  • if duodenal duodenal atrophy or lesions are discovered during the endoscopy
  • if duodenal lesions are discoverd at the histological examination

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Grenoble University Hospital

Grenoble, 38043, France

RECRUITING

Related Publications (31)

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    PMID: 17513438BACKGROUND
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    PMID: 7325229BACKGROUND
  • Breuillard C, Cynober L, Moinard C. Citrulline and nitrogen homeostasis: an overview. Amino Acids. 2015 Apr;47(4):685-91. doi: 10.1007/s00726-015-1932-2. Epub 2015 Feb 13.

    PMID: 25676932BACKGROUND
  • Osowska S, Moinard C, Neveux N, Loi C, Cynober L. Citrulline increases arginine pools and restores nitrogen balance after massive intestinal resection. Gut. 2004 Dec;53(12):1781-6. doi: 10.1136/gut.2004.042317.

    PMID: 15542514BACKGROUND
  • Osowska S, Duchemann T, Walrand S, Paillard A, Boirie Y, Cynober L, Moinard C. Citrulline modulates muscle protein metabolism in old malnourished rats. Am J Physiol Endocrinol Metab. 2006 Sep;291(3):E582-6. doi: 10.1152/ajpendo.00398.2005. Epub 2006 Apr 11.

    PMID: 16608884BACKGROUND
  • Faure C, Raynaud-Simon A, Ferry A, Dauge V, Cynober L, Aussel C, Moinard C. Leucine and citrulline modulate muscle function in malnourished aged rats. Amino Acids. 2012 Apr;42(4):1425-33. doi: 10.1007/s00726-011-0841-2. Epub 2011 Feb 23.

    PMID: 21344178BACKGROUND
  • Faure C, Morio B, Chafey P, Le Plenier S, Noirez P, Randrianarison-Huetz V, Cynober L, Aussel C, Moinard C. Citrulline enhances myofibrillar constituents expression of skeletal muscle and induces a switch in muscle energy metabolism in malnourished aged rats. Proteomics. 2013 Jul;13(14):2191-201. doi: 10.1002/pmic.201200262. Epub 2013 Jun 10.

    PMID: 23592530BACKGROUND
  • Ventura G, Noirez P, Breuille D, Godin JP, Pinaud S, Cleroux M, Choisy C, Le Plenier S, Bastic V, Neveux N, Cynober L, Moinard C. Effect of citrulline on muscle functions during moderate dietary restriction in healthy adult rats. Amino Acids. 2013 Nov;45(5):1123-31. doi: 10.1007/s00726-013-1564-3. Epub 2013 Aug 3.

    PMID: 23913268BACKGROUND
  • The economic burden of lung disease. European white lung book 2013:16-27.

    BACKGROUND
  • Antonione R. Nutrition in cardiac and pulmonary disease. In Basic in clinical nutrition. Sobotka L. ed. Galen, 4th ed. 485-493.

    BACKGROUND
  • Jonker R. and al. Whole body de novo ARG production and NO synthesis are reduced in COPD patients. Clin.Nutr. 2013;32(S1):S5-S6.

    BACKGROUND
  • Coeffier M, Miralles-Barrachina O, Le Pessot F, Lalaude O, Daveau M, Lavoinne A, Lerebours E, Dechelotte P. Influence of glutamine on cytokine production by human gut in vitro. Cytokine. 2001 Feb 7;13(3):148-54. doi: 10.1006/cyto.2000.0813.

    PMID: 11161457BACKGROUND
  • Lecleire S, Coeffier M, Leblond J, Hubert A, Lemoulan S, Petit A, Ducrotte P, Dechelotte P, Marion R. Modulation of nitric oxide and cytokines production by L-arginine in human gut mucosa. Clin Nutr. 2005 Jun;24(3):353-9. doi: 10.1016/j.clnu.2004.11.011.

    PMID: 15896421BACKGROUND
  • Hubert-Buron A, Leblond J, Jacquot A, Ducrotte P, Dechelotte P, Coeffier M. Glutamine pretreatment reduces IL-8 production in human intestinal epithelial cells by limiting IkappaBalpha ubiquitination. J Nutr. 2006 Jun;136(6):1461-5. doi: 10.1093/jn/136.6.1461.

    PMID: 16702304BACKGROUND
  • Reimund JM, Wittersheim C, Dumont S, Muller CD, Kenney JS, Baumann R, Poindron P, Duclos B. Increased production of tumour necrosis factor-alpha interleukin-1 beta, and interleukin-6 by morphologically normal intestinal biopsies from patients with Crohn's disease. Gut. 1996 Nov;39(5):684-9. doi: 10.1136/gut.39.5.684.

    PMID: 9026483BACKGROUND
  • Chan MF. Complications of upper gastrointestinal endoscopy. Gastrointest Endosc Clin N Am. 1996 Apr;6(2):287-303.

    PMID: 8673329BACKGROUND
  • Christensen M, Achiam M, Trap R, Stockel M, Rosenberg J, Schulze S. Transnasal gastroscopy. Dan Med Bull. 2000 Jun;47(3):218-20.

    PMID: 10913986BACKGROUND
  • Zubarik R, Eisen G, Mastropietro C, Lopez J, Carroll J, Benjamin S, Fleischer DE. Prospective analysis of complications 30 days after outpatient upper endoscopy. Am J Gastroenterol. 1999 Jun;94(6):1539-45. doi: 10.1111/j.1572-0241.1999.01141.x.

    PMID: 10364022BACKGROUND
  • Dumortier J, Ponchon T, Scoazec JY, Moulinier B, Zarka F, Paliard P, Lambert R. Prospective evaluation of transnasal esophagogastroduodenoscopy: feasibility and study on performance and tolerance. Gastrointest Endosc. 1999 Mar;49(3 Pt 1):285-91. doi: 10.1016/s0016-5107(99)70002-7.

    PMID: 10049409BACKGROUND
  • Lacy PD, Lee JM, O'Morain CA. Temporomandibular joint dislocation: an unusual complication of upper gastrointestinal endoscopy. Am J Gastroenterol. 2000 Dec;95(12):3653-4. doi: 10.1111/j.1572-0241.2000.03396.x. No abstract available.

    PMID: 11151916BACKGROUND
  • Kise Y, Suzuki R, Shimada H, Tanaka H, Oshiba G, Chino O, Makuuchi H. Idiopathic submucosal hematoma of esophagus complicated by dissecting aneurysm, followed-up endoscopically during conservative treatment. Endoscopy. 2001 Apr;33(4):374-8. doi: 10.1055/s-2001-13684.

    PMID: 11315902BACKGROUND
  • Vu CK, Korman MG, Bejer I, Davis S. Gastrointestinal bleeding after cold biopsy. Am J Gastroenterol. 1998 Jul;93(7):1141-3. doi: 10.1111/j.1572-0241.1998.346_e.x.

    PMID: 9672346BACKGROUND
  • Giudicelli R. [Esophageal perforations. Results of a national survey]. Ann Chir. 1992;46(2):183-7. No abstract available. French.

    PMID: 1605545BACKGROUND
  • Giangreco E, D'agate C, Barbera C, Puzzo L, Aprile G, Naso P, Bonanno G, Russo FP, Nicoletti A, Incarbone S, Trama G, Russo A. Prevalence of celiac disease in adult patients with refractory functional dyspepsia: value of routine duodenal biopsy. World J Gastroenterol. 2008 Dec 7;14(45):6948-53. doi: 10.3748/wjg.14.6948.

    PMID: 19058330BACKGROUND
  • Heresbach D, Napoléon B. Delchier J.C. and al. Consensus en endoscopie digestive. Acta endo (2009) 39 :206-2011.

    BACKGROUND
  • Prat F. Recommandations de la SFED 2005 : De la pratique des biopsies oeso-gastro-duodénales.

    BACKGROUND
  • Boustière C. Endoscopie digestive, antigoagulants, antiagrégants : faut-il encore modifier nos pratiques en 2013 ? Acta endo (2013) 43 :260-265.

    BACKGROUND
  • Boustiere C, Veitch A, Vanbiervliet G, Bulois P, Deprez P, Laquiere A, Laugier R, Lesur G, Mosler P, Nalet B, Napoleon B, Rembacken B, Ajzenberg N, Collet JP, Baron T, Dumonceau JM; European Society of Gastrointestinal Endoscopy. Endoscopy and antiplatelet agents. European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2011 May;43(5):445-61. doi: 10.1055/s-0030-1256317. Epub 2011 May 4.

    PMID: 21547880BACKGROUND
  • Recommandations de bonnes pratiques sur les antiagrégants plaquettaires: prise en compte des risques thrombotique et hémorragique en cas de geste endoscopique HAS-SFED, oct 2012.

    BACKGROUND
  • Napoleon B, Boneu B, Maillard L, Samama CM, Schved JF, Gay G, Ponchon T, Sautereau D, Canard JM; Board of the French Society for Digestive Endoscopy (SFED). Guidelines of the French Society for Digestive Endoscopy (SFED). Endoscopy. 2006 Jun;38(6):632-8. doi: 10.1055/s-2006-925086. Epub 2006 Mar 14. No abstract available.

    PMID: 16586249BACKGROUND
  • Ventura G, Moinard C, Sinico F, Carriere V, Lasserre V, Cynober L, De Bandt JP. Evidence for a role of the ileum in the control of nitrogen homeostasis via the regulation of arginine metabolism. Br J Nutr. 2011 Jul;106(2):227-36. doi: 10.1017/S0007114511000079.

    PMID: 22568979BACKGROUND

MeSH Terms

Conditions

HypoxiaInflammationPulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Signs and Symptoms, RespiratorySigns and SymptomsPathological Conditions, Signs and SymptomsPathologic ProcessesLung Diseases, ObstructiveLung DiseasesRespiratory Tract DiseasesChronic DiseaseDisease Attributes

Study Officials

  • Eric Fontaine, Professor

    Division of clinical Nutrition-Grenoble University Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Eric FONTAINE, Professor

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 28, 2016

First Posted

June 30, 2016

Study Start

January 1, 2016

Primary Completion

January 1, 2017

Study Completion

January 1, 2017

Last Updated

December 6, 2016

Record last verified: 2016-12

Data Sharing

IPD Sharing
Will not share

Locations