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

Sponsor

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

Overall Status

Recruiting

CT.gov ID

NCT04902235

Collaborator

Instituto de Salud Carlos III (Other)

Enrollment

Location

Arms

29.8

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypopituitarism Central Diabetes Insipidus Panhypopituitarism Psychological Disorder Social Isolation Hypothalamic Diseases Pituitary Diseases Oxytocin Deficiency	Drug: Experimental: CRH administration Drug: Control: Placebo administration	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

52 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Single-blind, randomized, placebo-controlled proof-of-concept studies with a crossover assignmentSingle-blind, randomized, placebo-controlled proof-of-concept studies with a crossover assignment

Masking:

Single (Participant)

Masking Description:

participants will be blinded to the intervention assignment

Primary Purpose:

Diagnostic

Official Title:

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

Actual Study Start Date :

Jul 6, 2021

Anticipated Primary Completion Date :

Apr 30, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

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)

Arm

Intervention/Treatment

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)

Outcome Measures

Primary Outcome Measures

Change in oxytocin concentration [Baseline blood exam (timepoint 0) and further blood collections after 15, 30, 45, 60, 90 and 120 minutes after baseline blood collection]
Change in oxytocin concentration (pg/mL) after administration of 1.0 µg/kg/body weight of CRH or 0.9% sodium chloride (NaCl)

Secondary Outcome Measures

Maximal change in oxytocin concentration (pg/mL) [Within the two hours after the injection]
Maximal change in oxytocin concentration (pg/mL) after administration of 1.0 µg/kg/body weight of CRH or 0.9% NaCl
Overall oxytocin secretion [Within the two hours after the injection]
Oxytocin area under the curve after administration of 1.0 µg/kg/body weight of CRH or 0.9% NaCl
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 cortisol concentration (nmol/L) after administration of 1.0 µg/kg/body weight of CRH or 0.9% NaCl
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]
Change in ACTH values (pmol/L) after administration of 1.0 µg/kg/body weight of CRH or 0.9% NaCl
Mood assessment [Baseline]
Correlation between Beck Depression Inventory-2 score (range from 0 to 63, higher scores mean a worse outcome) and baseline oxytocin concentration (pg/mL)
Quality of life assessment [Baseline]
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)
Impulsivity assessment [Baseline]
Correlation between Barratt Impulsiveness Scale (range from 30 to 120, higher scores indicate greater impulsivity) and baseline oxytocin concentration (pg/mL)
Alexithymia assessment [Baseline]
Correlation between Toronto Alexithymia scales-20 score (range from 20 to 100, higher scores mean a worse outcome) and baseline oxytocin concentration (pg/mL)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.