Clinical trial NCT04914806: Infantile NO Replenishment as a New Therapeutic Possibility
Official title: Association Between Premature Birth and Its Comorbidities With NO and the HPG Activation at Minipuberty
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Prematurity
Respiratory Distress Syndrome, Newborn
Keywords: preterm birth
neurodevelopment
cardiometabolic
minipuberty
Lead sponsor: National and Kapodistrian University of Athens
Sponsor class: OTHER
Collaborators: name: URI-NKUA
name: University Hospital, Lille
name: Centre Hospitalier Universitaire Vaudois
name: European Commission
First posted: 2021-06-07
Enrollment: 240
Sex: ALL
Minimum age (years): 1
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Preterm and full-term infants admitted to the Neonatal Unit due to respiratory distress.

Brief summary: Case-control study of inhaled Nitric Oxide (iNO) treatment of full-term and preterm infants. The main objective of this study is to investigate the association between premature birth and its later comorbidities (neuroendocrine, metabolic, cognitive, etc) with iNO treatment and the maturation of the HPG axis during minipuberty.

Detailed description: In preterm infants, inhaled NO (iNO) is routinely used to treat respiratory failure and pulmonary hypertension, while preclinical studies have shown that it markedly increases NO concentrations in the brain. Animal and human studies have shown that NO deficiency may jeopardize the establishment of a mature and functional HPG axis whereas it is also associated with a series of comorbidities affecting the overall brain development (e.g. sensory, fertility and cognitive functions). Prematurity has been associated with a series of non-communicable diseases of major importance in public health, including neurodevelopmental impairments, metabolic abnormalities (e.g. obesity, type 2 diabetes mellitus, impaired glucose tolerance) and cardiovascular disease. This study aims to evaluate the associations between altered minipuberty in preterm infants and the later development of multi-comorbidities (mental and non-mental disorders), and identify the possible implication of the NO pathway as a causative mechanism.

Specific objectives :

1. Assess the efficiency of NO replenishment therapy (i.e. role of NO pathway) as a therapeutic against alterations of minipuberty resulting from preterm birth.
2. Assess the efficiency of NO replenishment therapy (i.e. role of NO pathway) as a therapeutic against the multi-comorbidities (mental and non-mental disorders) related to altered minipuberty as a result of preterm birth.

Eligibility criteria: Inclusion Criteria:

* Preterm (GA\<37 weeks) or full-term (≥37 weeks of gestation) infants
* Requiring respiratory support
* Admitted to Neonatal Care Unit

Exclusion Criteria:

* Severe congenital anomalies
* Suspected major chromosomal anomalies
* Infants judged by the physician as nonviable

Primary outcomes:
measure: Gonadotrophin levels
timeFrame: up to 9 months of age
measure: Body fat and fat-free mass
timeFrame: up to 9 months of age
measure: HOMA-IR
timeFrame: up to 9 months
measure: Bayleys scale score
timeFrame: at 9 months of age
Secondary outcomes:
measure: Otoacoustic emissions
timeFrame: up to 9 months
measure: Fundoscopy
timeFrame: up to 9 months
measure: gusto-facial reflex
timeFrame: at 3 and 9 months of age
measure: Leptin levels
timeFrame: up to 9 months
Other outcomes:
Locations:
city: Lille
country: France
facility: Centre Hospitalier Regional Et Universitaire de Lille
city: Athens
country: Greece
facility: URI-NKUA
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
Study officials:
affiliation: URI-NKUA, Athens, Greece, 11527
name: George P. Chrousos, Professor
role: STUDY_CHAIR
References: