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

NCT04902235 | Completed Phase 4

• 1 other identifier: IIBSP-OXI-2020-101
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Change in oxytocin concentration

  Change in oxytocin concentration (pg/mL) after administration of 1.0 µg/kg/body weight of CRH or 0.9% sodium chloride (NaCl)

  Baseline blood exam (timepoint 0) and further blood collections after 15, 30, 45, 60, 90 and 120 minutes after baseline blood collection

Secondary Outcomes (8)

• Maximal change in oxytocin concentration (pg/mL)

  Within the two hours after the injection

• Overall oxytocin secretion

  Within the two hours after the injection

• Change in cortisol concentration (nmol/L)

  Baseline blood exam (timepoint 0) and further blood collections after 15, 30, 45, 60, 90 and 120 minutes after baseline blood collection

• Change in adrenocorticotropic hormone (ACTH) values

  Baseline blood exam (timepoint 0) and further blood collections after 15, 30, 45, 60, 90 and 120 minutes after baseline blood collection

• Mood assessment

  Baseline

Study Arms (2)

CRH administration

EXPERIMENTAL

Experimental: CRH administration

Drug: Experimental: CRH administration

Placebo administration

PLACEBO COMPARATOR

Control: Placebo administration

Drug: Control: Placebo administration

Interventions

Experimental: CRH administration 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

CRH administration

Control: Placebo administration 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)

Placebo administration

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau: lead
• Instituto de Salud Carlos III: collaborator

Study Sites (1)

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Related Publications (1)

• 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.

  PMID: 39824923 DERIVED

MeSH Terms

Conditions

Hypopituitarism; Diabetes Insipidus, Neurogenic; Combined Pituitary Hormone Deficiency; Mental Disorders; Social Isolation; Hypothalamic Diseases; Pituitary Diseases

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Diabetes Insipidus; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Social Behavior; Behavior

Study Officials

• Anna Aulinas, MD PhD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: participants will be blinded to the intervention assignment
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-blind, randomized, placebo-controlled proof-of-concept studies with a crossover assignment

Study Record Dates

• First Submitted: May 17, 2021
• First Posted: May 26, 2021
• Study Start: July 6, 2021
• Primary Completion: April 30, 2023
• Study Completion: May 1, 2023
• Last Updated: April 3, 2024

Record last verified: 2022-03

Locations

ES (1)