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

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

Status and phase: Completed; Phase 4

Conditions: Pituitary Diseases; Central Diabetes Insipidus; Psychological Disorder; Oxytocin Deficiency; Panhypopituitarism; Hypothalamic Diseases; Social Isolation; Hypopituitarism

Treatments: Drug: Control: Placebo administration; Drug: Experimental: GLP1-RA (exenatide) administration

Study type: Interventional

Funder types: Other

Identifiers

NCT04897802

IIBSP-OXI-2020-102

Details and patient eligibility

About

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.

Full 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.

Enrollment: 42 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts 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 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.

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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42 participants in 2 patient groups, including a placebo group

Experimental: GLP1-RA administration

Experimental group

Description:

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

Treatment:

Drug: Experimental: GLP1-RA (exenatide) administration

Control: Placebo administration

Placebo Comparator group

Description:

Sodium Chloride 0.9% will be administered subcutaneously at equivalent volume than GLP1-RA (exenatide) administration

Treatment:

Drug: Control: Placebo administration