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

Identification and Clinical Relevance of an Oxytocin Deficient State: a Randomized, Crossover, Placebo-controlled, Proof-of-concept Physiopathological Study (CRH Study)

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.

Study Overview

• Status: Completed
• Conditions: Pituitary Diseases; Hypothalamic Diseases; Hypopituitarism; Social Isolation; Panhypopituitarism; Psychological Disorder; Central Diabetes Insipidus; Oxytocin Deficiency
• Intervention / Treatment: Drug: Experimental: CRH administration; Drug: Control: Placebo administration

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.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Anna Aulinas, MD PhD; Phone Number: 7917 +34 932919000; Email: aaulinas@santpau.cat

Study Locations

• Spain
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CRH administration; Experimental: CRH administration	Drug: 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
Placebo Comparator: Placebo administration; Control: Placebo administration	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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal change in oxytocin concentration (pg/mL)	Maximal change in oxytocin concentration (pg/mL) after administration of 1.0 µg/kg/body weight of CRH or 0.9% NaCl	Within the two hours after the injection
Overall oxytocin secretion	Oxytocin area under the curve after administration of 1.0 µg/kg/body weight of CRH or 0.9% NaCl	Within the two hours after the injection
Change in cortisol concentration (nmol/L)	Change in cortisol concentration (nmol/L) after administration of 1.0 µg/kg/body weight of CRH or 0.9% NaCl	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	Change in ACTH values (pmol/L) after administration of 1.0 µg/kg/body weight of CRH or 0.9% NaCl	Baseline blood exam (timepoint 0) and further blood collections after 15, 30, 45, 60, 90 and 120 minutes after baseline blood collection
Mood assessment	Correlation between Beck Depression Inventory-2 score (range from 0 to 63, higher scores mean a worse outcome) and baseline oxytocin concentration (pg/mL)	Baseline
Quality of life assessment	Correlation between 36 item- Short Form Health Survey score (range from 0 to 100, the higher scores indicate better health status) and baseline oxytocin concentration (pg/mL)	Baseline
Impulsivity assessment	Correlation between Barratt Impulsiveness Scale (range from 30 to 120, higher scores indicate greater impulsivity) and baseline oxytocin concentration (pg/mL)	Baseline
Alexithymia assessment	Correlation between Toronto Alexithymia scales-20 score (range from 20 to 100, higher scores mean a worse outcome) and baseline oxytocin concentration (pg/mL)	Baseline

Collaborators and Investigators

• Sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Collaborators: Instituto de Salud Carlos III
• Investigators: Principal Investigator: Anna Aulinas, MD PhD, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2021
• Primary Completion (Actual): April 30, 2023
• Study Completion (Actual): May 1, 2023

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 20, 2021
• First Posted (Actual): May 26, 2021

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: oxytocin; cortisol; ACTH; central diabetes insipidus; panhypopituitarism; hypothalamus-pituitary diseases; corticorelin hormone
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pituitary Diseases; Mental Disorders; Hypopituitarism; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Hypothalamic Diseases
• Other Study ID Numbers: IIBSP-OXI-2020-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No