Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03368755
Other study ID # IUGR-CPET_PATRAS
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date January 8, 2018
Est. completion date January 30, 2022

Study information

Verified date April 2021
Source University of Patras
Contact Sotirios Fouzas, MD, PhD
Phone +302610999980
Email sfouzas@upatras.gr
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The study hypothesis is that intrauterine growth restriction (IUGR) may have long-term effects on respiratory muscle (RM) function, thus leading to reduced exercise capacity later in life. The objective is to investigate the above hypothesis by comparing RM function and cardiopulmonary exercise testing (CPET) parameters between school-aged children exposed to IUGR and healthy controls.


Description:

Introduction Epidemiological evidence supports the existence of a link between intrauterine growth restriction (IUGR) and reduced exercise capacity in young adulthood. Prolonged intrauterine hypoxia results in redistribution of fetal cardiac output towards the vital organs at the expense of skeletal muscles, and experimental data show that the muscles of animals exposed to IUGR may suffer permanent structural and functional changes. Prematurity, which often accompanies IUGR, is also associated with reduced exercise capacity later in life, supposedly due to airflow limitation, air trapping and/or reduced gas-exchange capacity. The respiratory muscles (RM) play a central role in the development (and perception) of locomotor muscle fatigue, which represents the major determinant of exercise limitation in otherwise healthy subjects. Heavy and/or sustained respiratory work leads to accumulation of metabolites in RM and triggers reflexes that increase the sympathetic vasoconstrictor outflow to the skeletal muscles, thus promoting fatigue. In support of the above concept, targeted RM training has been shown to increase the fatigability threshold and improve exercise performance. RM function can be assessed by means of strength and endurance, which can be estimated non-invasively by the maximum inspiratory and expiratory pressure (Pimax and Pemax), and the tension-time index (TTImus), respectively. TTImus is a composite parameter that reflects the balance between the capacity of RM and the load imposed upon them; high TTImus values indicate low endurance and increased risk of respiratory fatigue. In adults, impaired exercise tolerance is associated with reduced RM strength and endurance, both in normal and pathological conditions. However, similar data are not available in children. Hypothesis and objectives The study hypothesis is that IUGR may have long-term effects on RM function, thus leading to reduced exercise capacity later in life. Other factors, such as the presence and degree of respiratory dysfunction, the performance of the skeletal muscles and the nutritional status, may also be involved. The study objective is to investigate the above hypothesis by comparing RM function and cardiopulmonary exercise testing (CPET) parameters between school-aged children exposed to IUGR and healthy controls, taking also into account the aforementioned confounders. Methods Population In this case-control study, 50 school-aged children (7-10 years old) exposed to IUGR (birth weight <10th percentile & fetal ultrasound documentation) will be compared with 100 matched for age and gestational age controls. The study will be performed in the Pediatric CPET laboratory of the University Hospital of Patras, Greece, during a 2-year period (2018-2020). Participants will be recruited from the long-term follow-up program offered to all children who are born preterm or with IUGR, and from the local schools (healthy full-term controls). The protocol will be approved by the hospital Ethics Committee and parental informed consent will be obtained prior to enrollment. Protocol After a thorough review of the medical history, participants will undergo the following tests: 1. Nutritional status, body composition and skeletal muscle strength. Initially, weight and height will be measured, and the body mass index (BMI) will be calculated. Body composition (muscular mass, body fat, water) will be determined by the InBody 270 Body Composition Analyzer (Biospace, Seoul, Korea) using bioelectrical impedance analysis. Skeletal muscle strength (grasping power) will be measured using a digital grip dynamometer (Grip-D, TAKEI, Japan). 2. Lung function measurements. Spirometry, measurement of lung volumes (helium dilution technique) and measurement of lung diffusion capacity for carbon monoxide (DLCO) will be performed prior to CPET using the Jaeger MasterScreen PFT device (CareFusion, San Diego, USA). Spirometric measurements will be repeated at 5, 10, and 15 minutes after CPET. 3. RM function. Pimax, Pemax, airway pressure at 100 msec after occlusion (P0.1), and Ti and Ttot will be measured by the Micro 5000 device (Medisoft, Sorinnes, Belgium) according to the guidelines. TTImus will be calculated as (Pimean / Pimax) x (Ti / Ttot), where Pimean is the mean airway pressure resulting from the formula Pimean = 5 x P0.1 x Ti. RM function will be determined a) prior to CPET, b) during CPET when the anaerobic threshold (AT) will be reached, and c) after CPET, when heart rate (HR) and oxygen consumption will be normalized (recovery period). 4. CPET. CPET will be performed by the Ultima CPX system (Medgraphics, St. Paul, USA), using a cycle ergometer and according to a standardized protocol11 and the established guidelines. The following parameters will be recorded: total work in Watts, maximum HR, maximum oxygen consumption (VO2max), AT indices (work, HR, VO2 ) and duration of recovery. Statistical analysis Between-group comparisons will be performed with Student's t or Mann-Whitney U test, as appropriate. Linear regression analysis will be used to explore the relationship between RM function and CPET parameters, after adjustment for nutritional status, body composition, lung function, and prematurity. The trend of Pimax, Pemax, and TTImus changes during CPET (baseline - AT - recovery) will be also assessed and compared between groups. The analyses will be performed using the IBM SPSS version 23.0 (IBM Corp., Armonk, NY). Innovation and implications The study will be the first to explore whether IUGR is associated with impaired exercise tolerance in childhood due to RM dysfunction, while taking into account the confounding effect of prematurity, impaired lung function, body composition and nutritional status. Should the relationship IUGR - RM dysfunction - exercise limitation be confirmed, it will provide new insights on the long-term effects of IUGR; impaired exercise tolerance may lead to reduced physical activity, thus enhancing the well-known metabolic and cardiovascular consequences of IUGR later in life. In this regard, the findings of this study may assist in identifying children at risk and planning targeted strategies to improve exercise capacity in this vulnerable population.


Recruitment information / eligibility

Status Recruiting
Enrollment 150
Est. completion date January 30, 2022
Est. primary completion date December 31, 2021
Accepts healthy volunteers No
Gender All
Age group 7 Years to 10 Years
Eligibility Inclusion Criteria: - (Cases) School-aged children (7-10 years old) exposed to IUGR (birth weight <10th percentile & fetal ultrasound documentation) - (Controls) School-aged children (7-10 years old) NOT exposed to IUGR (birth weight >10th percentile) Exclusion Criteria: - Disability - Congenital heart disease - Current (active) respiratory infection

Study Design


Intervention

Diagnostic Test:
Cardiopulmonary Exercise Testing
Pimax, Pemax, airway pressure at 100 msec after occlusion (P0.1), and Ti and Ttot will be measured by the Micro 5000 device (Medisoft, Sorinnes, Belgium). TTImus will be calculated as (Pimean / Pimax) x (Ti / Ttot), where Pimean is the mean airway pressure resulting from the formula Pimean = 5 x P0.1 x Ti9. RM function will be determined a) prior to CPET, b) during CPET when the anaerobic threshold (AT) will be reached, and c) after CPET, when heart rate (HR) and oxygen consumption will be normalized.
Respiratory Muscle Strength and Endurance
CPET will be performed by the Ultima CPX system (Medgraphics, St. Paul, USA), using a cycle ergometer and according to a standardized protocol. The following parameters will be recorded: total work in Watts, maximum HR, maximum oxygen consumption (VO2max), AT indices (work, HR, VO2 ) and duration of recovery.

Locations

Country Name City State
Greece University Hospital of Patras Patras

Sponsors (2)

Lead Sponsor Collaborator
University of Patras European Society for Paediatric Research (ESPR)

Country where clinical trial is conducted

Greece, 

References & Publications (12)

American Thoracic Society/European Respiratory Society. ATS/ERS Statement on respiratory muscle testing. Am J Respir Crit Care Med. 2002 Aug 15;166(4):518-624. — View Citation

Dempsey JA, Romer L, Rodman J, Miller J, Smith C. Consequences of exercise-induced respiratory muscle work. Respir Physiol Neurobiol. 2006 Apr 28;151(2-3):242-50. Review. — View Citation

Foglio K, Clini E, Facchetti D, Vitacca M, Marangoni S, Bonomelli M, Ambrosino N. Respiratory muscle function and exercise capacity in multiple sclerosis. Eur Respir J. 1994 Jan;7(1):23-8. — View Citation

Godfrey S. Exercise Testing in Children. London, UK: WB Saunders Company Ltd., 1974.

Kilbride HW, Gelatt MC, Sabath RJ. Pulmonary function and exercise capacity for ELBW survivors in preadolescence: effect of neonatal chronic lung disease. J Pediatr. 2003 Oct;143(4):488-93. — View Citation

Lane RH, Chandorkar AK, Flozak AS, Simmons RA. Intrauterine growth retardation alters mitochondrial gene expression and function in fetal and juvenile rat skeletal muscle. Pediatr Res. 1998 May;43(5):563-70. — View Citation

Lane RH, Maclennan NK, Daood MJ, Hsu JL, Janke SM, Pham TD, Puri AR, Watchko JF. IUGR alters postnatal rat skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1 gene expression in a fiber specific manner. Pediatr Res. 2003 Jun;53(6):994-1000. Epub 2003 Mar 19. — View Citation

McConnell AK. CrossTalk opposing view: respiratory muscle training does improve exercise tolerance. J Physiol. 2012 Aug 1;590(15):3397-8; discussion 3399-400. doi: 10.1113/jphysiol.2012.235572. — View Citation

Regamey N, Moeller A. Paediatric exercise testing. Eur Respir Mon 2010; 47: 291-309

Rosenberg A. The IUGR newborn. Semin Perinatol. 2008 Jun;32(3):219-24. doi: 10.1053/j.semperi.2007.11.003. — View Citation

Ross MG, Beall MH. Adult sequelae of intrauterine growth restriction. Semin Perinatol. 2008 Jun;32(3):213-8. doi: 10.1053/j.semperi.2007.11.005. Review. — View Citation

Svedenkrans J, Henckel E, Kowalski J, Norman M, Bohlin K. Long-term impact of preterm birth on exercise capacity in healthy young men: a national population-based cohort study. PLoS One. 2013 Dec 6;8(12):e80869. doi: 10.1371/journal.pone.0080869. eCollection 2013. — View Citation

* Note: There are 12 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary VO2 max Maximum O2 consumption, in ml/kg/min. The index will be compared between IUGR and controls. 1 day (during exercise testing)
Primary TTmus Tension-time index of the respiratory muscles. No values (ratio). The index will be compared between IUGR and controls. 1 day (during exercise testing)
See also
  Status Clinical Trial Phase
Completed NCT04506970 - Predicting Placental Pathologies by Ultrasound Imaging
Recruiting NCT03866863 - Intra Uterine Growth Restriction
Recruiting NCT03662178 - Investigating the Structured Use of Ultrasound Scanning for Fetal Growth
Not yet recruiting NCT05720169 - Fetal, Obstetrics and Reproduction Genomics
Completed NCT04633551 - Vascular Inflammation and Anti-inflammatory Supplements After Adverse Pregnancy Outcomes N/A
Recruiting NCT05500989 - PlacEntal Acute Atherosis RefLecting Subclinical Atherosclerosis
Recruiting NCT04141189 - Comparison of Follow-up Protocols in Terms of Fetal, Neonatal and Maternal Results in Intrauterine Growth Retardation N/A
Completed NCT03726697 - Effect of Tahneek on Hypoglycemia in Newborn Infants N/A
Recruiting NCT03398629 - Diagnosis and Management of Intrauterine Growth Restriction and Congenital Anomalies
Recruiting NCT02473991 - Correlation Between Placental Thickness in the Second and Third Trimester and Fetal Weight N/A
Completed NCT02696577 - The Effect of Omega 3 on Pregnancy Complicated by Asymmetrical Intrauterine Growth Restriction Phase 2
Recruiting NCT04766866 - sFlt1/PlGF and Planned Delivery to Prevent Preeclampsia at Term. N/A
Terminated NCT04047966 - Study of the Fetal and Maternal Microbiota in Preganant Women With Fetal Defect Growth
Not yet recruiting NCT03865628 - Ultrasound Evaluation of Fetal Hemodynamics and Perinatal Complications
Completed NCT05328453 - Sonographic 3D Measurement of Fetal Thymus May be Used to Predict the Small Baby in Pregnancy.
Completed NCT05800938 - The Effect of Oral Isosorbide Mononitrate Therapy on Umbilical Artery Doppler Resistance Index in Pregnancies With Intrauterine Growth Restriction: Prospective Randomized Control Trial Phase 4
Not yet recruiting NCT06226051 - Growing Little PEAPODS Study
Recruiting NCT02807324 - Women Specific Cardiac Recovery After Preeclampsia
Recruiting NCT02515292 - Evaluation of Infants With Intrauterine Growth Restriction N/A
Active, not recruiting NCT01942525 - Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants N/A