Sleep Disorders in Hypothalamic and Pituitary Damage
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18-70
SponsorFundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
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).
Trial 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.
Trial design
Design model
Case-control
Time perspective
Cross-sectional
Treatments tested in this trial
This is an observational study. No drugs will be administered
Other interventionData 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.
Treatment groups
60 Participants
are divided into 2 treatment groupsGroup A: Patients with hypopituitarism and hypothalamic damage with or without vasopressin deficiency1 intervention
Group B: Healthy controls1 intervention
Trial outcomes
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)
Time frame
From enrollment to completion of the assessments at 3 monthsSecondary outcomes
1
Saliva oxytocin concentrations in patients compared to controls
* Oxytocin samples will be collected at 6:00 a.m., 12:00 p.m., 6:00 p.m., and 11:00 p.m. * Correlations between oxytocin concentrations and sleep disorders will be performed.
Time frame
From day 1 and day 2 of the objective sleep assessments (polisomnography and MSLT)2
Urine 6-sulfametoxymelatonin concentrations in patients compared to controls
* Samples will be collected at 9:00 p.m., 6:00 a.m., 12:00 p.m., and 5:00 p.m in urine. * Correlations between 6-sulfametoxymelatonin concentrations and sleep disorders will be performed.
Time frame
From day 1 and day 2 of the objective sleep assessments (polisomnography and MSLT)3
Prevalence of Brain structural and perfusion abnormalities using Magnetic Resonance Imaging in patients compared to controls
ROI related to sleep (e.g thalamus, cortex, amygdala) will be defined; gray matter hyperintensities will be quantified from the FLAIR image; DTI will calculate diffusor tensor parameters (FA, mean, axial and radial diffusivity) across the whole brain. Brain structural and perfusion abnormalities will be correlated with sleep measures
Time frame
From enrollment to completion of the assessment at 3 months4
Prevalence of glucose brain metabolism abnormalities using Fluorodeoxyglucose Positron Emission Tomography in patients and controls
Glucose brain metabolism will be quantified at ROI. Brain glucose metabolism will be correlated with sleep measures
Time frame
From enrollment to completion of the assessment at 3 monthsSponsors and contacts
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Source ClinicalTrials.gov