Identification and Clinical Relevance of an Oxytocin Deficient State (GLP1 Study)

Identification and Clinical Relevance of an Oxytocin Deficient State: a Randomized, Crossover, Placebo-controlled, Proof-of-concept, Physiopathological Study (GLP1 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, glucagon-like peptide 1 (GLP1) has shown to increase OT release.

This study is designed to evaluate OT values after administration of GLP1 in adults (healthy volunteers and patients with hypopituitarism).

The investigators hypothesize that OT response will be blunted following GLP1 receptor agonist (GLP1-RA) 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: GLP1-RA (exenatide) 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 (GLP1-RA 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): 42
• Phase: Phase 4

Contacts and Locations

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 amino transferase (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
• Any type of diabetes mellitus
• Obese patients on GLP1-RA therapies
• 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 GLP1-RA
• 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: Experimental: GLP1-RA administration; A single dose of 10 mcg of GLP1-RA (exenatide) will be injected subcutaneously and samples will be collected over 2 hours (15 (T15), 30 (T30), 45 (T45), 60 (T60'), 90 (T90) and 120 (T120) minutes) after GLP1-RA:placebo administration to assess OT secretory patterns	Drug: Experimental: GLP1-RA (exenatide) administration; a single dose of 10 mcg of GLP-RA (exenatide) will be administered subcutaneously and samples to assess OT secretory patterns will be collected over 2 hours; Other Names: exenatide administration
Placebo Comparator: Control: Placebo administration; Sodium Chloride 0.9% will be administered subcutaneously at equivalent volume than GLP1-RA (exenatide) administration	Drug: Control: Placebo administration; Sodium Chloride 0.9% will be administered subcutaneously at equivalent volume than 10 mcg of exenatide; Other Names: placebo administration (sodium chloride)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in oxytocin concentration (pg/mL)	Change in oxytocin concentration (pg/mL) after administration of 10 µg of GLP1-RA (exenatide) 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)	Change in oxytocin concentration (pg/mL) after administration of 10 µg of GLP1-RA (exenatide) or 0.9% NaCl	Within the two hours after the injection
Overall oxytocin secretion (pg/mL)	Oxytocin area under the curve after administration of 10 µg of GLP1-RA (exenatide) or 0.9% NaCl	Within the two hours after the injection
Change in glucose concentration (mg/dL)	Change in glucose concentration (mg/dL) after administration of 10 µg of GLP1-RA (exenatide) 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 insulin concentration (pmol/L)	Change in insulin concentration (pmol/L) after administration of 10 µg of GLP1-RA (exenatide) 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	Association 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	Association 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	Association between Barratt Impulsiveness Scale (range from 30 to 120, higher scores indicate greater impulsivity) and baseline oxytocin concentration (pg/mL)	Baseline
Alexithymia assessment	Association 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, IR-Sant Pau

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2021
• Primary Completion (Actual): April 30, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 20, 2021
• First Posted (Actual): May 24, 2021

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: oxytocin; exenatide; psychopathology; diabetes insipidus; hypopituitarism; hypothalamic-pituitary diseases
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Behavior; Social Behavior; Mental Disorders; Pituitary Diseases; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Hypopituitarism; Hypothalamic Diseases; Combined Pituitary Hormone Deficiency; Social Isolation; Health Services Administration; Peptides; Amino Acids, Peptides, and Proteins; Biological Factors; Inorganic Chemicals; Chlorine Compounds; Complex Mixtures; Toxins, Biological; Sodium Compounds; Chlorides; Hydrochloric Acid; Venoms; Exenatide; Sodium Chloride; Organization and Administration
• Other Study ID Numbers: IIBSP-OXI-2020-102

Drug and device information, study documents

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