Identification and Clinical Relevance of an Oxytocin Deficient State (CRH Study)

NCT ID: NCT04902235

Last Updated: 2024-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-06
• Study Completion Date: 2023-05-01

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.

Conditions

Hypopituitarism; Central Diabetes Insipidus; Panhypopituitarism; Psychological Disorder; Social Isolation; Hypothalamic Diseases; Pituitary Diseases; Oxytocin Deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: SINGLE

Study Groups

CRH administration

Experimental: CRH administration

Group Type: EXPERIMENTAL

Experimental: CRH administration

Intervention Type: DRUG

CRH at 1.0 µg/kg/body weight will be injected intravenously as a bolus over 30 seconds and samples will be collected over 2 hours (15 (T15), 30 (T30), 45 (T45), 60 (T60'), 90 (T90) and 120 (T120) minutes) after CRH:placebo administration to assess OT secretory patterns

Placebo administration

Control: Placebo administration

Group Type: PLACEBO_COMPARATOR

Control: Placebo administration

Intervention Type: DRUG

Sodium Chloride 0.9% will be administered intravenously as a bolus over 30 seconds at equivalent volume than CRH administration (1.0 µg/kg/body weight)

Interventions

Experimental: CRH administration

CRH at 1.0 µg/kg/body weight will be injected intravenously as a bolus over 30 seconds and samples will be collected over 2 hours (15 (T15), 30 (T30), 45 (T45), 60 (T60'), 90 (T90) and 120 (T120) minutes) after CRH:placebo administration to assess OT secretory patterns

Intervention Type: DRUG

Control: Placebo administration

Sodium Chloride 0.9% will be administered intravenously as a bolus over 30 seconds at equivalent volume than CRH administration (1.0 µg/kg/body weight)

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Instituto de Salud Carlos III

OTHER_GOV

Sponsor Role: collaborator

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anna Aulinas, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Locations

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Countries

Spain

References

Asla Q, Garrido M, Urgell E, Terzan S, Santos A, Fernandez M, Varghese N, Atila C, Calabrese A, Biagetti B, Plessow F, Gich I, Christ-Crain M, Eckert A, Webb SM, Lawson EA, Aulinas A. Oxytocin levels in response to CRH administration in hypopituitarism and hypothalamic damage: a randomized, crossover, placebo-controlled trial. Sci Rep. 2025 Jan 18;15(1):2360. doi: 10.1038/s41598-025-86566-y.

Reference Type: DERIVED

PMID: 39824923 (View on PubMed)

Other Identifiers

IIBSP-OXI-2020-101

Identifier Type: -

Identifier Source: org_study_id