Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Non Invasive Evaluation of Muscle Hypoxia in COPD Patient (EVANIMUS) (EVANIMUS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03921983
Recruitment Status : Not yet recruiting
First Posted : April 19, 2019
Last Update Posted : April 19, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Clermont-Ferrand

Brief Summary:

Peripheral muscle oxidative function is altered in COPD(chronic obstrutive pulmonary disease) patients. Multiple factors could contribute to this dysfunction including chronic hypoxia and deconditioning (sedentarity).

The evaluation of mitochondrial function is based on invasive method (muscle biopsy and in vitro respirometry) or magnetic resonance spectroscopy limited to small muscle groups. Recently, a non invasive method has been described using Near InfraRed Spectroscopy (NIRS). During arterial occlusion, muscle deoxygenation is only dependent of local oxygen consumption. The time constant recovery (k) of the deoxygenation during repeated ischemia periods has been shown to be correlated to measurements of maximal mitochondrial capacity.

k is lower in COPD patients compared to smokers without bronchial obstruction. However, the influence of arterial hypoxia has never been studied precisely, no more than the confounding effect of deconditioning on k.

So , the aim is to compare k in COPD patients with chronic hypoxemia (treated with long term oxygenotherapy, LTOT+ group) and patients without hypoxia, matched for their physical activity (LTOT- group).

The hypothe is that k will be lower in LTOT+ group compared to LTOT- group and that short term O2 supplementation will improve it, which would suggest a muscle hypoxia. By contrast, O2 should not influence k in LOT- group, in whom it is mainly determined by muscle conditioning.


Condition or disease Intervention/treatment Phase
COPD (Chronic Obstructive Pulmonary Disease) Hypoxemia Other: Oxygen supplementation Not Applicable

Detailed Description:

Investigator will compare mVO2 time constant in 2 groups of COPD (chronic obstrutive pulmonary disease) patients matched for age, sex, physical activity (estimated by GPAQ questionnaire (Global Physical Activity Questionnaire)), one with chronic hypoxemia (LTOT+ group) and one without blood gas abnormalities (LTOT- group)..

Inclusion visit It will allow to calculate physical activity in Mets.min/week, from the GPAQ questionnaire. The patient will also be accustomed to the repeated arterial occlusion procedure. A pneumatic cuff will be wrapped around the thigh and will be progressively inflated to a suprasystolic value (rapid air inflation system Hokanson), from 160 mmHg up to tolerated maximal pressure (max 220 mmHg).

Experimental visit

  • Muscle biopsy. A biopsy of the vastus lateralis will be performed while breathing ambient air. After disinfection and anesthesia of skin and subcutaneous tissue, an automatic biopsy gun (Monopty Bard 14G) will be introduced in the muscle and a 20 mg biopsy will be withdrawn. The maximal mitochondrial O2 consumption and mitochondrial affinity for O2 will be immediately measured with high resolution respirometry (Oroboros, 10 mg tissue). A 10 mg fragment will be stored in liquid nitrogen for mRNA analysis of hypoxia driven genes (Hypoxia-inducible Factor 1, Vascular Endothelial Growth Factor, Carbonic Anhydrase 9, Heme Oxygenase 1).
  • mVO2 time constant measurement (k, min-1) in ambient air. A NIRS probe (Oxymon III) will be placed on the thigh (contralateral to the muscle biopsy) and secured with an elastic wrap. The NIRS signal will be displayed continuously and recorded on a software (Oxysoft) The inflation cuff will be placed upstream the NIRS probe. After 5 to 10 isometric contractions of the quadriceps, the cuff will be rapidly inflated (maximal tolerated pressure determined during the inclusion visit) and deflated according to a predetermined protocol: 5 s /5 s 5 times, followed by 7 s /7 s 5 times and then 10 s/10 s 10 times. The deoxygenation kinetics (% deoxygenation/min) will be calculated for every occlusion and these deoxygenation indices will be expressed over time in order to calculate the time constant of the exponential relationship (k, min-1). This sequence will be repeated twice and the k values will be averaged.
  • mVO2 time constant measurement with O2. Oxygen therapy will be given to the patient for 1 hour before repeating the k determination as described above. Oxygen flow will be set to the habitual flow rate in the LTOT+ group, and an arbitrary 3 L/min flow rate in the LTOT- group.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: measurements will be made with and without short term oxygen supplementation
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Non Invasive Evaluation of Muscle Hypoxia in Chronic Obstructive Pulmonary Disease Patient
Estimated Study Start Date : July 1, 2019
Estimated Primary Completion Date : January 1, 2020
Estimated Study Completion Date : December 31, 2020

Arm Intervention/treatment
Experimental: LTOT +
COPD patients with long term oxygenotherapy
Other: Oxygen supplementation
short term O2 supplementation during 1 hour

Active Comparator: LTOT -
COPD patients without chronic hypoxemia (no LTOT)
Other: Oxygen supplementation
short term O2 supplementation during 1 hour




Primary Outcome Measures :
  1. mVO2 recovery time constant (k) measured while breathing ambient air [ Time Frame: day 1 ]
    Time constant (min-1) of NIRS muscle oxygenation kinetics following repetitive arterial occlusions


Secondary Outcome Measures :
  1. variation of k with oxygen supplementation [ Time Frame: day 1 ]
    Difference of the time constant (k, min-1) between 2 conditions: ambient air and with oxygen supplementation

  2. Mitochondrial affinity for O2 [ Time Frame: day 1 ]
    Apparent K (µmol O2/min/g tissue) measured with respirometry on permeabilized muscle fibers at decreasing concentration of O2



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • COPD diagnostic
  • Both sex
  • 18 <Age <80 years old
  • LTOT- group : PaO2 ≥ 65 mmHg and SaO2≥ 92%
  • LTOT+ group: long term oxygenotherapy prescribed for more than 3 months, with daily use between 12 and 15 hours.

Patients in both groups will be matched for age (± 5 years), sex and physical activity estimated by GPAQ questionnaire (± 15% Mets.min/week).

Exclusion Criteria:

  • Recent cardiorespiratory exacerbation (<6 weeks).
  • Pulmonary rehabilitation program during the last 2 months
  • Continuous LTOT (24 hours) or deambulation O2 therapy alone
  • Anticoagulant drugs
  • Hematocrit outside the normal range (35-50%)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03921983


Contacts
Layout table for location contacts
Contact: Lise LACLAUTRE +334.75754963 promo_interne_drci@chu-clermontferrand.fr

Locations
Layout table for location information
France
CHU de Clermont-Ferrand Not yet recruiting
Clermont-Ferrand, France, 63000
Contact: Lise LACLAUTRE    +33473754963    promo_interne_drci@chu-clermontferrand.fr   
Principal Investigator: Frédéric Costes, MD, PhD         
Sub-Investigator: Ruddy Richard         
Sponsors and Collaborators
University Hospital, Clermont-Ferrand
Investigators
Layout table for investigator information
Principal Investigator: Frédériv Costes, MD, PhD University Hospital, Clermont-Ferrand

Layout table for additonal information
Responsible Party: University Hospital, Clermont-Ferrand
ClinicalTrials.gov Identifier: NCT03921983     History of Changes
Other Study ID Numbers: RBHP 2018 COSTES
2018-A02206-49 ( Other Identifier: 2018-A02206-49 )
First Posted: April 19, 2019    Key Record Dates
Last Update Posted: April 19, 2019
Last Verified: April 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Clermont-Ferrand:
muscle oxygenation
hypoxia
mitochondrial function
non invasive
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Hypoxia
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms