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

Primary Purpose

Hypopituitarism, Central Diabetes Insipidus, Panhypopituitarism

Status
Recruiting
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Experimental: CRH administration
Control: Placebo administration
Sponsored by
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Hypopituitarism focused on measuring oxytocin, panhypopituitarism, central diabetes insipidus, hypothalamus-pituitary diseases, cortisol, ACTH, corticorelin hormone

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Hospital de la Santa Creu i Sant PauRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

CRH administration

Placebo administration

Arm Description

Experimental: CRH administration

Control: Placebo administration

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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
Overall oxytocin secretion
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)
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
Change in ACTH values (pmol/L) after administration of 1.0 µg/kg/body weight of CRH or 0.9% NaCl
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)
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)
Impulsivity assessment
Correlation between Barratt Impulsiveness Scale (range from 30 to 120, higher scores indicate greater impulsivity) and baseline oxytocin concentration (pg/mL)
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)

Full Information

First Posted
May 17, 2021
Last Updated
March 18, 2022
Sponsor
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Collaborators
Instituto de Salud Carlos III
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1. Study Identification

Unique Protocol Identification Number
NCT04902235
Brief Title
Identification and Clinical Relevance of an Oxytocin Deficient State (CRH Study)
Official Title
Identification and Clinical Relevance of an Oxytocin Deficient State: a Randomized, Crossover, Placebo-controlled, Proof-of-concept Physiopathological Study (CRH Study)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 6, 2021 (Actual)
Primary Completion Date
April 30, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Collaborators
Instituto de Salud Carlos III

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Model Description
Single-blind, randomized, placebo-controlled proof-of-concept studies with a crossover assignment
Masking
Participant
Masking Description
participants will be blinded to the intervention assignment
Allocation
Randomized
Enrollment
52 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CRH administration
Arm Type
Experimental
Arm Description
Experimental: CRH administration
Arm Title
Placebo administration
Arm Type
Placebo Comparator
Arm Description
Control: Placebo administration
Intervention Type
Drug
Intervention Name(s)
Experimental: CRH administration
Intervention Description
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
Intervention Name(s)
Control: Placebo administration
Intervention Description
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)
Primary Outcome Measure Information:
Title
Change in oxytocin concentration
Description
Change in oxytocin concentration (pg/mL) after administration of 1.0 µg/kg/body weight of CRH or 0.9% sodium chloride (NaCl)
Time Frame
Baseline blood exam (timepoint 0) and further blood collections after 15, 30, 45, 60, 90 and 120 minutes after baseline blood collection
Secondary Outcome Measure Information:
Title
Maximal change in oxytocin concentration (pg/mL)
Description
Maximal change in oxytocin concentration (pg/mL) after administration of 1.0 µg/kg/body weight of CRH or 0.9% NaCl
Time Frame
Within the two hours after the injection
Title
Overall oxytocin secretion
Description
Oxytocin area under the curve after administration of 1.0 µg/kg/body weight of CRH or 0.9% NaCl
Time Frame
Within the two hours after the injection
Title
Change in cortisol concentration (nmol/L)
Description
Change in cortisol concentration (nmol/L) after administration of 1.0 µg/kg/body weight of CRH or 0.9% NaCl
Time Frame
Baseline blood exam (timepoint 0) and further blood collections after 15, 30, 45, 60, 90 and 120 minutes after baseline blood collection
Title
Change in adrenocorticotropic hormone (ACTH) values
Description
Change in ACTH values (pmol/L) after administration of 1.0 µg/kg/body weight of CRH or 0.9% NaCl
Time Frame
Baseline blood exam (timepoint 0) and further blood collections after 15, 30, 45, 60, 90 and 120 minutes after baseline blood collection
Title
Mood assessment
Description
Correlation between Beck Depression Inventory-2 score (range from 0 to 63, higher scores mean a worse outcome) and baseline oxytocin concentration (pg/mL)
Time Frame
Baseline
Title
Quality of life assessment
Description
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)
Time Frame
Baseline
Title
Impulsivity assessment
Description
Correlation between Barratt Impulsiveness Scale (range from 30 to 120, higher scores indicate greater impulsivity) and baseline oxytocin concentration (pg/mL)
Time Frame
Baseline
Title
Alexithymia assessment
Description
Correlation between Toronto Alexithymia scales-20 score (range from 20 to 100, higher scores mean a worse outcome) and baseline oxytocin concentration (pg/mL)
Time Frame
Baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anna Aulinas, MD PhD
Phone
+34 932919000
Ext
7917
Email
aaulinas@santpau.cat
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anna Aulinas, MD PhD
Organizational Affiliation
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital de la Santa Creu i Sant Pau
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Aulinas, MD PhD
Phone
+34932919000
Ext
7917
Email
aaulinas@santpau.cat
First Name & Middle Initial & Last Name & Degree
Claudia Delgado
Phone
+34932919000
Ext
7634
Email
cdelgadoe@santpau.cat

12. IPD Sharing Statement

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

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