Sleep Disorders in Hypothalamic and Pituitary Damage

NCT07143266 | Recruiting

• 1 other identifier: IIBSP-SUE-2024-36
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Hypothalamus has a key role in multiple vital functions, including regulation of sleep-wake cycles. Oxytocin (OT), a neurohormone synthetized in the hypothalamus, has a wide range of physiological functions, including a putative role in improving sleep quality. Hypothalamic and pituitary damage (HPD) is associated with a clinically relevant OT deficient state and multiple and severe comorbidities including poor sleep quality, that have a well-known negative impact on general health and quality of life (QoL). Several factors may coexist in the pathophysiology of sleep disorders (SD) in HPD and SD might be a keystone in the persistence of some of the comorbidities observed in HPD. Therefore, appropriate identification and understanding of the mechanisms contributing to SD in HPD is mandatory to choose adequate preventive strategies and treatment. This project is aimed to (1) identify the prevalence of SD in HPD, (2) to determine OT role in sleep quality and (3) to identify potential mechanisms and mediators of sleep quality and their associations with clinical outcomes in patients with HPD with the ultimate goal of identifying preventive and therapeutic targets. We will use a controlled cross-sectional design of patients with HPD and sex-, BMI-, age- matched controls and an innovative cross-disciplinary approach bridging neuroendocrinology, psychology, neurophysiology, neuroimaging, nuclear medicine and neuroophthalmology disciplines to learn about the prevalence of SD in HPD and to disentangle the underpinning mechanisms behind SDs in HPD. The results of this project will be an extremely important step towards optimizing therapy for patients with HPD who have higher mortality and poor QoL despite appropriate hormone replacement therapy.

Conditions

Hypopituitarism; Sleep Wake Disorders; Hypothalamic Diseases; Oxytocin Deficiency

Keywords

Sleep Disorder; Oxytocin deficiency; Hypopituitarism; Hypothalamic damage

Outcome Measures

Primary Outcomes (1)

• Prevalence of sleep disorders in patients with hypothalamic and pituitary damage compared to healthy controls

  Prevalence (%) of patients with sleep disorders (assessed by objective and subjective measures of sleep): * Impaired sleep quality assessed by Pittsburgh Sleep Quality Index (PSQI) and nocturnal polisomnography (PSG) * Daytime sleepiness assessed by Epworth Sleepiness Scale (ESS) * Obstructive Sleep Apnea (OSA) assessed by Berlin Questionnaire (BQ), Stop- BANG score risk and PSG * Insomnia assessed by Severity Index (ISI). * Daytime Sleepiness assessed by Multiple Sleep Latency Test (MSLT)

  From enrollment to completion of the assessments at 3 months

Secondary Outcomes (5)

• Saliva oxytocin concentrations in patients compared to controls

  From day 1 and day 2 of the objective sleep assessments (polisomnography and MSLT)

• Urine 6-sulfametoxymelatonin concentrations in patients compared to controls

  From day 1 and day 2 of the objective sleep assessments (polisomnography and MSLT)

• Prevalence of Brain structural and perfusion abnormalities using Magnetic Resonance Imaging in patients compared to controls

  From enrollment to completion of the assessment at 3 months

• Prevalence of glucose brain metabolism abnormalities using Fluorodeoxyglucose Positron Emission Tomography in patients and controls

  From enrollment to completion of the assessment at 3 months

• Prevalence of patients with neuroophthalmological damage (in patients with HPD only) assessed by an expert neuro-ophthalmologist

  Baseline

Study Arms (2)

Patients with hypopituitarism and hypothalamic damage with or without vasopressin deficiency

Differences between those patients with vasopressin deficiency (AVP-D) and those without AVP-D will be analyzed.

Other: This is an observational study. No drugs will be administered

Healthy controls

Similar age, and BMI than the study group (patients with hypopituitarism) and matched by sex.

Other: This is an observational study. No drugs will be administered

Interventions

This is an observational study. No drugs will be administered OTHER

Data from objective sleep evaluation (actigraphy, polisomnography and MLST), subjective sleep evaluation (questionnaires), neuroimaging (MRI and PET-CT), ophthalmological evaluation and hormone evaluation (urine and blood) will be collected in a cross-sectional manner, without performing any additional intervention.

Healthy controls; Patients with hypopituitarism and hypothalamic damage with or without vasopressin deficiency

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The patients will be recruited from the Research Center for Pituitary Diseases and the Neurosurgery Department at the Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

You may qualify if:

• Patients with hypothalamic-pituitary dysfunction (HPD) with at least one pituitary hormone deficiency and at least one clinical sign of hypothalamic damage (e.g., arginine-vasopressin deficiency (AVP-D) and/or severe obesity and/or hyperphagia; MRI suggestive of hypothalamic damage; traumatic brain injury; radiotherapy in the sellar region and/or brain tumors affecting the hypothalamus).
• Healthy controls matched for BMI, age, and sex.

You may not qualify if:

• Poor control of hormonal deficiencies in the previous 6 months.
• Use of new psychoactive drugs in the last 3 months or occasional use.
• Clinically significant liver, lung, kidney, and cardiovascular disease.
• Any neurological condition affecting brain function (stroke, dementia, uncontrolled epilepsy with recent seizures).
• Uncontrolled diabetes mellitus.
• Active psychosis.
• Ophthalmology: total blindness, Glaucoma, uveitis, visual acuity \<0.6, or eye surgery in the previous 6 months.
• Any acute illness that the investigator determines may interfere with study participation or safety.
• Pregnancy or breastfeeding.
• Patients who refuse or are unable to provide written informed consent.
• In controls: presence of brain or pituitary tumor, radiation involving the hypothalamus or pituitary, and history of hypopituitarism.

Sponsors & Collaborators

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

Study Sites (1)

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

RECRUITING

MeSH Terms

Conditions

Hypopituitarism; Sleep Wake Disorders; Hypothalamic Diseases

Condition Hierarchy (Ancestors)

Pituitary Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders

Study Officials

• Anna Aulinas, MD PhD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna Aulinas, MD PhD

CONTACT

+34932919000; aaulinas@santpau.cat

Alejandra Espinosa

CONTACT

+34932919000; aespinosag@santpau.cat

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Target Duration: 3 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2025
• First Posted: August 27, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: November 18, 2025

Record last verified: 2025-09

Locations

ES (1)