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CompletedNCT02021903HYPOSOMNPARKUpdated Aug 25, 2020

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

An interventional study of V1: HGPO + meal and V2: placebo + meal and V1: placebo 75mg + meal and V2: HGPO 75mg + meal in Parkinsonian Disorders, sponsored by University Hospital, Toulouse. Completed at 2 sites in France. Open to participants aged 35 Years to 85 Years. Per ClinicalTrials.gov, last updated 2020-08-25.

Sponsored by University Hospital, Toulouse · Not applicable, Interventional, and Diagnostic

Phase
Not applicable
Study type
Interventional
Enrollment
21
Allocation
Randomized
Ages
35 Years to 85 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Parkinsonian Disorders

Keywords

  • arterial hypotension
  • postprandial sleepiness
  • orthostatic hypotension
  • synucleinopathies
  • hyperglycemia
03

Who can participate

Ages eligible
35 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Not applicable
Primary purpose
Diagnostic
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Investigator)
Enrollment
21 participants (actual)

Study arms

  • Experimental
    HGPO + Placebo

    V1: HGPO 75 mg + meal and V2: Placebo 75 mg + meal

    Other: V1: HGPO + meal and V2: placebo + 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

Interventions

  • OtherV1: 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

    Also known as: V1: HGPO 75mg + meal and V2: placebo 75mg + meal

  • OtherV1: 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

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 2 hours

Secondary outcomes

  1. 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 ;

    Time frame: 120 minutes

  2. 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 ;

    Time frame: 120 minutes

  3. 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;

    Time frame: 120 minutes

  4. 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)

    Time frame: 120 minutes

  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.

    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

06

Study locations

2 sites
  • UHBordeaux
    Bordeaux, 33076, France
  • UHToulouse
    Toulouse, 31059, France
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT02021903
Lead sponsor
University Hospital, Toulouse
Collaborators
Ministry of Health, France
Responsible party
Sponsor
First posted
Dec 27, 2013
Start date
May 2012
Primary completion
Dec 20, 2019
Completion
Jun 2020
Last update
Aug 25, 2020

Study contacts

Anne Pavy-Le Traon, MD
principal investigator · University Hospital, Toulouse

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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