Post-prandial Hypotension and Sleepiness in Parkinson's Disease and Other Synucleinopathies

Parkinsonian Disorders Clinical Trial

— HYPOSOMNPARK  

Official title:

Post-prandial Hypotension and Sleepiness in Parkinson's Disease and Other Synucleinopathies: the Model of an Oral Glucose Load

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02021903
• Other study ID #: 1120008
• Status: Completed
• Phase: N/A
• Start date: May 2012
• Est. completion date: June 2020

Study information

• Verified date: August 2020
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Excessive daytime sleepiness (EDS) is observed in 30 to 50 % of patients with Parkinson's disease (PD) patients, Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA). It is a major complain and represents a socially relevant problem as unintended episodes of sleep can also occur while driving for example. Arterial hypotension is frequently observed in patients with PD, DLB and MSA and considered as a marker of autonomic failure. Sleepiness is known to occur preferentially when patients are having arterial hypotension whatever the cause (i.e. postprandial period, administration of hypotensive medication such as dopamine agonists). We hypothesize that arterial hypotension is associated with abnormal sleepiness. We have observed this association in an on-going epidemiological survey Hyperglycaemia induced by oral glucose load - a standardized model simulating food intake during a meal - provokes arterial hypotension in the majority of Parkinson's disease patients with dysautonomia. It can be hypothesised that sleep attacks in these patients could be mediated by this fall in blood pressure.

Description:

Excessive daytime sleepiness (EDS) is observed in 30 to 50 % of patients with Parkinson's disease (PD) patients, Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA). It is a major complain and represents a socially relevant problem as unintended episodes of sleep can also occur while driving for example. The exact pathophysiology of EDS in PD, DLB and MSA has not been fully elucidated so far, although pharmacological factors (dopaminergic medications) and pathological factors (neurodegeneration of sleep-wakefulness regulatory areas) have been identified. Arterial hypotension is frequently observed in patients with PD, DLB and MSA and considered as a marker of autonomic failure. Sleepiness is known to occur preferentially when patients are having arterial hypotension whatever the cause (i.e. postprandial period, administration of hypotensive medication such as dopamine agonists). We hypothesize that arterial hypotension is associated with abnormal sleepiness. We have observed this association in an on-going epidemiological survey (COPARK Cohort of 800 PD patients, manuscript in preparation). Hyperglycaemia induced by oral glucose load - a standardized model simulating food intake during a meal - provokes arterial hypotension in the majority of Parkinson's disease patients with dysautonomia. It can be hypothesised that sleep attacks in these patients could be mediated by this fall in blood pressure.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: June 2020
• Est. primary completion date: December 20, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 85 Years

Eligibility

Inclusion Criteria:

• Aged 35 to 85

• Parkinson's disease patients (UKPDSBB diagnostic criteria), patients with Dementia with Lewy Bodies (DLB consortium criteria, Mc Keith et al. 2005) or patients with Multiple System Atrophy (Gilman's criteria, 2008) complaining of a post-prandial sleepiness interfering with their daily living and with orthostatic hypotension

• Stable antiparkinsonian treatments (including those for dysautonomia) for the 2 months before the study and during the entire study

• Signed written informed consent for the present study

• Social security insurance coverage

Exclusion Criteria:

• atypical or secondary parkinsonism

• patients without excessive daytime sleepiness

• inability to give a consent due to severe cognitive dysfunction

• severe depression

• Deep brain stimulation treatment

• Moderate to severe obstructive sleep apnoea/hypopnoea syndrome or other co-morbidities that could account for abnormal daytime sleepiness

• Severe primary or secondary insomnia

• Treatment with sedative medications (unless moderate and stable treatment for more than 2 months before entering the study and maintained at stable dosage during all the study)

• Diabetes mellitus

• Systolic arterial pressure at rest in seated position lower than 100 mmHg in sitting position

• Pregnancy and suckling

Related Conditions & MeSH terms

• Hypotension
• Parkinson Disease
• Parkinsonian Disorders
• Sleepiness

Intervention

Other:
• V1: HGPO + meal and V2: placebo + meal
Ambulatory polysomnography for the night preceding each test Usual antiparkinsonian treatments at their usual dose and timing Randomisation to receive an oral solution of glucose load or a placebo (fructose). Standard meal 4 hours after the test During two hours following the oral solution administration and the standardized meal, we will perform the followings for each patient : continuous digital blood pressure monitoring by Nexfin® blood pressure monitoring at brachial artery continuous polysomnographic recording synchronized continuous digital audiovisual recording glucose and insulin blood level monitoring Additional blood samples will be taken in order to assay the intestine-pancreatic neuropeptides including incretins GLP- 1 and GIP
• V1: placebo 75mg + meal and V2: HGPO 75mg + meal
Ambulatory polysomnography for the night preceding each test Usual antiparkinsonian treatments at their usual dose and timing Randomisation to receive an oral solution of glucose load or a placebo (fructose). Standard meal 4 hours after the test During two hours following the oral solution administration and the standardized meal, we will perform the followings for each patient : continuous digital blood pressure monitoring by Nexfin® blood pressure monitoring at brachial artery continuous polysomnographic recording synchronized continuous digital audiovisual recording glucose and insulin blood level monitoring Additional blood samples will be taken in order to assay the intestine-pancreatic neuropeptides including incretins GLP- 1 and GIP

Locations

Country	Name	City	State
France	UHBordeaux	Bordeaux
France	UHToulouse	Toulouse

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Toulouse	Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of patients presenting a "sleep onset"	Rate of patients presenting a "sleep onset", defined as the occurrence of at least 30 s of sleep at polysomnography or at patient's recall) with or without occurrence of hypotension (defined as a drop in systolic blood pressure level of at least 20 mmHg) during the 2 hours following oral glucose load or placebo fructose.	2 hours
Secondary	rate of patients without arterial hypotension nor a sleep episode within 120 minutes after oral solution administration ;	rate of patients without arterial hypotension nor a sleep episode within 120 minutes after oral solution administration ;	120 minutes
Secondary	rate of patients that show a sleep episode but without arterial hypotension within 120 minutes after oral solution administration ;	rate of patients that show a sleep episode but without arterial hypotension within 120 minutes after oral solution administration ;	120 minutes
Secondary	rate of patients that show arterial hypotension within 120 minutes after oral solution administration but not a sleep episode;	rate of patients that show arterial hypotension within 120 minutes after oral solution administration but not a sleep episode;	120 minutes
Secondary	Occurrence of arterial hypotension and a sleep episode within 120 minutes following a standardized meal	Occurrence of arterial hypotension (defined as a drop in systolic blood pressure level of at least 20 mmHg and a sleep episode (defined according to video-polygraphic parameters) within 120 minutes following a standardized meal (at lunch time)	120 minutes
Secondary	Changes in intestine-pancreatic neuropeptides including incretins (GLP-1 - GIP) following an oral glucose load, placebo fructose load, or standardized meal - correlation with the post-prandial BP drop.	Changes in intestine-pancreatic neuropeptides including incretins (GLP-1 - GIP) following an oral glucose load, placebo fructose load, or standardized meal - correlation with the post-prandial BP drop.	120 minutes