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

Identification and Clinical Relevance of an Oxytocin Deficient State Following Melatonin Administration in Patients With Hypopituitarism: a Proof-of-concept, Physiopathological Study With a Control Group

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, melatonin has shown to increase OT release.

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

The investigators hypothesize that OT response will be blunted following melatonin in patients with hypopituitarism compared to healthy controls.

Study Overview

• Status: Completed
• Conditions: Hypopituitarism; Social Isolation; Pituitary Dysfunction; Hypothalamic Obesity; Central Diabetes Insipidus; Oxytocin Deficiency
• Intervention / Treatment: Dietary supplement: Melatonin

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

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: 16 years and older (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

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 melatonin
• patients refusing or unable to give written informed consent
• patients receiving fluvoxamine and/or impossibility to stop hypnotics 48 hours prior to the study visit.
• 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: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with hypopituitarism; A single dose of melatonin administration	Dietary supplement: Melatonin; A single dose of melatonin (1.9 mg)
Active Comparator: Healthy controls; A single dose of melatonin administration	Dietary supplement: Melatonin; A single dose of melatonin (1.9 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in oxytocin concentration	Change in oxytocin concentration (pg/mL) after administration of 1.9 mg of melatonin orally.	Baseline blood exam (timepoint 0) and further blood collections after 30, 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)	Maximal change in oxytocin concentration (pg/mL) after administration of 1.9 mg of melatonin administered orally.	Within the two hours after the injection
Overall oxytocin secretion	Oxytocin area under the curve after administration of 1.9 melatonin administered orally	Within the two hours after the injection
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)	At baseline
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)	At baseline
Impulsivity assessment	Correlation between Barratt Impulsiveness Scale (range from 30 to 120, higher scores indicate greater impulsivity) and baseline oxytocin concentration (pg/mL)	At baseline
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)	At baseline

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Actual): September 1, 2023
• Study Completion (Actual): November 1, 2023

Study Registration Dates

• First Submitted: March 17, 2022
• First Submitted That Met QC Criteria: March 31, 2022
• First Posted (Actual): April 8, 2022

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: melatonin; oxytocin; hypopituitarism; vasopresin deficiency
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Hypothalamic Diseases; Pituitary Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hypopituitarism; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: IIBSP-OXI-2021-112

Drug and device information, study documents

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