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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University Hospital, Toulouse
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by (Responsible Party):
University Hospital, Toulouse
ClinicalTrials.gov Identifier:
NCT02021903
First received: December 20, 2013
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

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 Intervention
Parkinsonian Patients
Post-prandial Sleepiness
Orthostatic Hypotension
Other: V1: HGPO + meal and V2: placebo + meal
Other: V1: placebo 75mg + meal and V2: HGPO 75mg + meal

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by University Hospital, Toulouse:

Primary Outcome Measures:
  • Rate of patients presenting a "sleep onset" [ Time Frame: 2 hours ] [ Designated as safety issue: Yes ]
    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:
  • rate of patients without arterial hypotension nor a sleep episode within 120 minutes after oral solution administration ; [ Time Frame: 120 minutes ] [ Designated as safety issue: Yes ]
    rate of patients without arterial hypotension nor a sleep episode 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 ; [ Time Frame: 120 minutes ] [ Designated as safety issue: Yes ]
    rate of patients that show a sleep episode but without arterial hypotension within 120 minutes after oral solution administration ;

  • rate of patients that show arterial hypotension within 120 minutes after oral solution administration but not a sleep episode; [ Time Frame: 120 minutes ] [ Designated as safety issue: Yes ]
    rate of patients that show arterial hypotension within 120 minutes after oral solution administration but not a sleep episode;

  • Occurrence of arterial hypotension and a sleep episode within 120 minutes following a standardized meal [ Time Frame: 120 minutes ] [ Designated as safety issue: Yes ]
    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)

  • 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 ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 24
Study Start Date: May 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: V1: placebo 75mg + meal and V2: HGPO 75mg + meal

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.

  Eligibility

Ages Eligible for Study:   35 Years to 85 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02021903

Contacts
Contact: Anne Pavy-Le Traon, MD 0561772271 ext 33 pavy-letraon.a@chu-toulouse.fr

Locations
France
UHBordeaux Active, not recruiting
Bordeaux, France, 33076
UHToulouse Recruiting
Toulouse, France, 31059
Contact: Anne Pavy-Le Traon, MD    0561772271      
Sponsors and Collaborators
University Hospital, Toulouse
Ministry of Health, France
Investigators
Principal Investigator: Anne Pavy-Le Traon, MD University Hospital, Toulouse
  More Information

No publications provided

Responsible Party: University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT02021903     History of Changes
Other Study ID Numbers: 1120008
Study First Received: December 20, 2013
Last Updated: July 22, 2014
Health Authority: France: Agence Nationale de Sécurité des Médicaments et des Produits de Santé

Keywords provided by University Hospital, Toulouse:
arterial hypotension
parkinson's disease
postprandial sleepiness
orthostatic hypotension
synucleinopathies
hyperglycemia

Additional relevant MeSH terms:
Autonomic Nervous System Diseases
Primary Dysautonomias
Hypotension
Hypotension, Orthostatic
Parkinson Disease
Basal Ganglia Diseases
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Orthostatic Intolerance
Parkinsonian Disorders
Vascular Diseases

ClinicalTrials.gov processed this record on October 20, 2014