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

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau42 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

SINGLE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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)

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 Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: Baseline

Impulsivity assessment

Association between Barratt Impulsiveness Scale (range from 30 to 120, higher scores indicate greater impulsivity) and baseline oxytocin concentration (pg/mL)

Time frame: 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)

Time frame: Baseline

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes