Post-prandial Hypotension and Sleepiness in Parkinson's Disease and Other Synucleinopathies
Condition: Parkinsonian Disorders
MeSH terms: Parkinson Disease; Parkinsonian Disorders; Synucleinopathies; Hypotension; Sleepiness
Study type: Interventional

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.
    

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.
    

Intervention name(s): V1: HGPO + meal and V2: placebo + meal; V1: placebo 75mg + meal and V2: HGPO 75mg + meal
Intervention type(s): Other; Other
Intervention description(s): 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; 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 intervention name(s): V1: HGPO 75mg + meal and V2: placebo 75mg + meal
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Diagnostic
Keywords: arterial hypotension; postprandial sleepiness; orthostatic hypotension; synucleinopathies; hyperglycemia