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

Social Isolation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04902235
• Other study ID #: IIBSP-OXI-2020-101
• Status: Completed
• Phase: Phase 4
• Start date: July 6, 2021
• Est. completion date: May 1, 2023

Study information

• Verified date: March 2022
• Source: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: May 1, 2023
• Est. primary completion date: April 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Central Diabetes Insipidus
• Diabetes Insipidus
• Hypopituitarism
• Mental Disorders
• Oxytocin Deficiency
• Panhypopituitarism
• Pituitary Diseases
• Psychological Disorder
• Social Isolation

Intervention

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
• 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)

Locations

Country	Name	City	State
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau	Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Impulsivity assessment	Correlation between Barratt Impulsiveness Scale (range from 30 to 120, higher scores indicate greater impulsivity) and baseline oxytocin concentration (pg/mL)	Baseline
Secondary	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