Clinical trial NCT04902235: Identification and Clinical Relevance of an Oxytocin Deficient State (CRH Study)
Official title: Identification and Clinical Relevance of an Oxytocin Deficient State: a Randomized, Crossover, Placebo-controlled, Proof-of-concept Physiopathological Study (CRH Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypopituitarism
Central Diabetes Insipidus
Panhypopituitarism
Psychological Disorder
Social Isolation
Hypothalamic Diseases
Pituitary Diseases
Oxytocin Deficiency
Keywords: oxytocin
panhypopituitarism
central diabetes insipidus
hypothalamus-pituitary diseases
cortisol
ACTH
corticorelin hormone
Lead sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Sponsor class: OTHER
Collaborators: name: Instituto de Salud Carlos III
First posted: 2021-05-26
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Single-blind, randomized, placebo-controlled proof-of-concept studies with a crossover assignment
Primary purpose: DIAGNOSTIC

Brief summary: Oxytocin (OT) is a hypothalamic peptide that enters the peripheral circulation via the posterior pituitary gland. OT plays a key role in regulating appetite, psychopathology, prosocial behavior and sexual function. Hypopituitarism is associated with increased obesity, increased psychopathology, sexual and prosocial dysfunction despite appropriate hormone replacement. A few studies suggest the existence of a possible OT deficient state in hypopituitarism. In animal models, corticorelin hormone (CRH) has shown to increase OT release.

This study is designed to evaluate oxytocin values after administration of CRH in adults (healthy volunteers and patients with hypopituitarism).

The investigators hypothesize that OT response will be blunted following CRH in patients with hypopituitarism compared to healthy controls.

Detailed description: This research is focused on two groups of participants: healthy controls (HC) and hypopituitary patients (HYPO) with at least one symptom of hypothalamic damage, presumably at highest risk for OT deficiency.

The aim is to improve knowledge on the physiology and patho-physiology of endogenous OT secretion in hypopituitary patients compared to healthy controls using a randomized, single-blind, crossover assignment (CRH vs placebo), placebo-control design.

Clinical implications of secretory OT dynamics and release under different stimuli using validated questionnaires to evaluate psychopathology, socio-emotional functioning, disordered eating behavior, impaired quality of life and sexual dysfunction, will be also evaluated.

Eligibility criteria: Inclusion Criteria:

* Patients with hypopituitarism (HYPO) (\>1 pituitary hormone deficiency) and stable hormone replacement for the prior three months
* At least one clinical sign of hypothalamic damage
* Female participants will be done in the early to midfollicular phase

Exclusion Criteria:

* uncorrected hormone deficiency
* creatinine \>1.5mg/dL
* alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.5x upper limit of normal
* hematocrit less than 30%
* suicidality or active psychosis
* participation in a trial with investigational drugs within 30 days
* using a high glucocorticoid dose
* vigorous physical exercise
* alcohol intake within 24 hours before the study participation
* evidence of any acute illness or any illness that the Investigator determines could interfere with study participation or safety
* pregnancy or breastfeeding for last 8 weeks
* known allergies towards CRH
* patients refusing or unable to give written informed consent
* Additionally for healthy controls: the presence of brain or pituitary tumor, radiation involving the hypothalamus or pituitary, history of hypopituitarism or receiving testosterone or glucocorticoids esters.

Primary outcomes:
measure: Change in oxytocin concentration
timeFrame: Baseline blood exam (timepoint 0) and further blood collections after 15, 30, 45, 60, 90 and 120 minutes after baseline blood collection
Secondary outcomes:
measure: Maximal change in oxytocin concentration (pg/mL)
timeFrame: Within the two hours after the injection
measure: Overall oxytocin secretion
timeFrame: Within the two hours after the injection
measure: Change in cortisol concentration (nmol/L)
timeFrame: Baseline blood exam (timepoint 0) and further blood collections after 15, 30, 45, 60, 90 and 120 minutes after baseline blood collection
measure: Change in adrenocorticotropic hormone (ACTH) values
timeFrame: Baseline blood exam (timepoint 0) and further blood collections after 15, 30, 45, 60, 90 and 120 minutes after baseline blood collection
measure: Mood assessment
timeFrame: Baseline
measure: Quality of life assessment
timeFrame: Baseline
measure: Impulsivity assessment
timeFrame: Baseline
measure: Alexithymia assessment
timeFrame: Baseline
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
Study officials:
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: Anna Aulinas, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: