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

Sponsor

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

Overall Status

Recruiting

CT.gov ID

NCT04897802

Collaborator

Instituto de Salud Carlos III (Other)

Enrollment

Location

Arms

27.6

Anticipated Duration (Months)

1.9

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, 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.

Condition or Disease	Intervention/Treatment	Phase
Hypopituitarism Central Diabetes Insipidus Panhypopituitarism Psychological Disorder Social Isolation Hypothalamic Diseases Pituitary Diseases Oxytocin Deficiency	Drug: Experimental: GLP1-RA (exenatide) 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 (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 Design

Study Type:

Interventional

Anticipated Enrollment :

52 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Single (Participant)

Primary Purpose:

Diagnostic

Official Title:

Identification and Clinical Relevance of an Oxytocin Deficient State: a Randomized, Crossover, Placebo-controlled, Proof-of-concept, Physiopathological Study (GLP1 Study)

Actual Study Start Date :

Sep 13, 2021

Anticipated Primary Completion Date :

Apr 30, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

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
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

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

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

Outcome Measures

Primary Outcome Measures

Change in oxytocin concentration (pg/mL) [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 10 µg of GLP1-RA (exenatide) or 0.9% sodium chloride (NaCl)

Secondary Outcome Measures

Maximal change in oxytocin concentration (pg/mL) [Within the two hours after the injection]
Change in oxytocin concentration (pg/mL) after administration of 10 µg of GLP1-RA (exenatide) or 0.9% NaCl
Overall oxytocin secretion (pg/mL) [Within the two hours after the injection]
Oxytocin area under the curve after administration of 10 µg of GLP1-RA (exenatide) or 0.9% NaCl
Change in glucose concentration (mg/dL) [Baseline blood exam (timepoint 0) and further blood collections after 15, 30, 45, 60, 90 and 120 minutes after baseline blood collection]
Change in glucose concentration (mg/dL) after administration of 10 µg of GLP1-RA (exenatide) or 0.9% NaCl
Change in insulin concentration (pmol/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 insulin concentration (pmol/L) after administration of 10 µg of GLP1-RA (exenatide) or 0.9% NaCl
Mood assessment [Baseline]
Association 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]
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)
Impulsivity assessment [Baseline]
Association between Barratt Impulsiveness Scale (range from 30 to 120, higher scores indicate greater impulsivity) and baseline oxytocin concentration (pg/mL)
Alexithymia assessment [Baseline]
Association 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 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.