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

Study Overview
=================
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, 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.

Official Title
-----------------
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

Conditions
-----------------
Oxytocin Deficiency, Hypopituitarism, Hypothalamic Obesity, Pituitary Dysfunction, Central Diabetes Insipidus, Social Isolation

Intervention / Treatment
-----------------
* Dietary Supplement: Melatonin


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with hypopituitarism<br>A single dose of melatonin administration | Dietary Supplement: Melatonin<br>* A single dose of melatonin (1.9 mg)<br>|
| Active Comparator: Healthy controls<br>A single dose of melatonin administration | Dietary Supplement: Melatonin<br>* A single dose of melatonin (1.9 mg)<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
oxytocin, melatonin, hypopituitarism, vasopresin deficiency