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

NCT02021903 | Completed

• 1 other identifier: 1120008
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

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.

Conditions

Parkinsonian Disorders

Keywords

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

Outcome Measures

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.

  2 hours

Secondary Outcomes (5)

• rate of patients without arterial hypotension nor a sleep episode within 120 minutes after oral solution administration ;

  120 minutes

• rate of patients that show a sleep episode but without arterial hypotension within 120 minutes after oral solution administration ;

  120 minutes

• rate of patients that show arterial hypotension within 120 minutes after oral solution administration but not a sleep episode;

  120 minutes

• Occurrence of arterial hypotension and a sleep episode within 120 minutes following a standardized meal

  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.

  120 minutes

Study Arms (2)

HGPO + Placebo

EXPERIMENTAL

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

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

Placebo + HGPO

PLACEBO COMPARATOR

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

Other: V1: placebo 75mg + meal and V2: HGPO 75mg + meal

Interventions

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

* 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

HGPO + Placebo

V1: placebo 75mg + meal and V2: HGPO 75mg + meal OTHER

* 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

Placebo + HGPO

Eligibility Criteria

• Age: 35 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Toulouse: lead
• Ministry of Health, France: collaborator

Study Sites (2)

UHBordeaux

Bordeaux, 33076, France

Location

UHToulouse

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Parkinsonian Disorders; Hypotension; Hypotension, Orthostatic; Synucleinopathies; Hyperglycemia

Interventions

Meals

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Vascular Diseases; Cardiovascular Diseases; Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Glucose Metabolism Disorders

Intervention Hierarchy (Ancestors)

Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Anne Pavy-Le Traon, MD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2013
• First Posted: December 27, 2013
• Study Start: May 1, 2012
• Primary Completion: December 20, 2019
• Study Completion: June 1, 2020
• Last Updated: August 25, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)