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

• ClinicalTrials.gov Identifier: NCT02021903
• Recruitment Status: Completed
• First Posted: December 27, 2013
• Last Update Posted: August 25, 2020
• Sponsor: University Hospital, Toulouse
• Collaborator: Ministry of Health, France
• Information provided by (Responsible Party): University Hospital, Toulouse

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Parkinsonian Disorders	Other: V1: HGPO + meal and V2: placebo + meal; Other: V1: placebo 75mg + meal and V2: HGPO 75mg + meal	Not Applicable

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Diagnostic
• Official Title: Post-prandial Hypotension and Sleepiness in Parkinson's Disease and Other Synucleinopathies: the Model of an Oral Glucose Load
• Study Start Date: May 2012
• Actual Primary Completion Date: December 20, 2019
• Actual Study Completion Date: June 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: HGPO + Placebo; V1: HGPO 75 mg + meal and V2: Placebo 75 mg + meal	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; Other Name: V1: HGPO 75mg + meal and V2: placebo 75mg + meal
Placebo Comparator: Placebo + HGPO; V1: Placebo 75 mg + meal and V2: HGPO 75 mg + meal	Other: 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

Outcome Measures

Primary Outcome Measures :

1. Rate of patients presenting a "sleep onset" [ Time Frame: 2 hours ]
   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.

Secondary Outcome Measures :

1. rate of patients without arterial hypotension nor a sleep episode within 120 minutes after oral solution administration ; [ Time Frame: 120 minutes ]
   rate of patients without arterial hypotension nor a sleep episode within 120 minutes after oral solution administration ;
2. rate of patients that show a sleep episode but without arterial hypotension within 120 minutes after oral solution administration ; [ Time Frame: 120 minutes ]
   rate of patients that show a sleep episode but without arterial hypotension within 120 minutes after oral solution administration ;
3. rate of patients that show arterial hypotension within 120 minutes after oral solution administration but not a sleep episode; [ Time Frame: 120 minutes ]
   rate of patients that show arterial hypotension within 120 minutes after oral solution administration but not a sleep episode;
4. Occurrence of arterial hypotension and a sleep episode within 120 minutes following a standardized meal [ Time Frame: 120 minutes ]
   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)
5. 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. [ Time Frame: 120 minutes ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 35 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

France

UHBordeaux

Bordeaux, France, 33076

UHToulouse

Toulouse, France, 31059

Sponsors and Collaborators

University Hospital, Toulouse

Ministry of Health, France

Investigators

• Principal Investigator: Anne Pavy-Le Traon, MD; University Hospital, Toulouse

More Information

• Responsible Party: University Hospital, Toulouse
• ClinicalTrials.gov Identifier: NCT02021903
• Other Study ID Numbers: 1120008
• First Posted: December 27, 2013
• Last Update Posted: August 25, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Toulouse:

arterial hypotension; postprandial sleepiness; orthostatic hypotension; synucleinopathies; hyperglycemia

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Hypotension; Sleepiness; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases; Vascular Diseases; Cardiovascular Diseases