To explore the safety and feasibility of continuous and intermittent hypoxia therapy in PD and the differences of symptom modification of different hypoxia protocols. Secondary outcomes include exploring the responsiveness of subjective and…
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
As this is an exploratory study, primary outcomes are multidimensional and
assess safety as well as feasibility of this study:
- Nature and total number of adverse events (including vital parameters
abnormalities)
- Feasibility questionnaire (including feasibility questionnaire sum score)
- Sensitivity (change) of secondary outcome measures pre- and postintervention
Secondary outcome
Secondary
- Self-reported overall symptom impression and one important or
altitude-responsive symptom chosen by participant on Likert scale 1-10
(allowing half points), as well as urge to take dopaminergic medication on
usual moments of intake, on 10-point scale ranging from *substantially less* to
*substantially more* (allowing half points).
- Bradykinesia quantified using a Modified Perdue pegboard test)
- Mobility (Timed Up & Go Test, steps and time)
- Balance (MiniBES test, totaal- en subscore)
- Movement Disorder Society-Unified Parkinson*s Disease Rating Scale
(MDS-UPDRS) part III (sum score and individual elements)
- Finger tapping test (amount of taps and errors)
- Accelerometry registration of hand tremor (with Movisens Move 4
accelerometer)
- Non-motor symptoms (stress, mood, anxiety, pain, fatigue) on Likert scale
1-10 (allowing half points).
- Heartrate variability (using Polar smartwatch)
Lab outcomes:
- Serum platelet-derived growth factor receptor β (PDGFRβ) from baseline ABG
and last ABG during intervention (fifth ABG including baseline)
- Serum cortisol before and after baseline clinical assessment, and three ABGs
(between directly post-intervention and +-40 minutes post-intervention).
- Serum erythropoietin before baseline and last blood gas (+- 40 minutes
post-intervention).
- Venous blood gas at baseline and blood draw at the end of the intervention
Other characteristics and effect modifiers:
- Baseline characteristics (age, gender, PD severity (Hoehn and Yahr), disease
duration, quality of life (Parkinson*s Disease Questionnaire 39-PDQ39),
pulmonary function testing, diffusion capacity (DLCO), p0.1, MIP, other
medication (e.g. beta-antagonists)
- Potential effect modifiers (measured before every intervention): levodopa
equivalent daily dose, sleep (item 9 of PSQI), physical activity (IPAQ-SF)
Background summary
Anecdotal evidence suggests that visiting high-altitude areas improves motor
symptoms of Parkinson's disease (PD). It is hypothesized that the positive
effect of altitude on the symptoms of PD results from decreased oxygen pressure
at high altitudes that leads to adaptive mechanisms that influence PD symptoms.
This will be assessed in an exploratory phase I trial, which will additionally
address the potential of strong inter-individual differences of modification of
symptoms by altitude simulation, and for the identification of the optimal
protocol to simulate high-altitude.
Study objective
To explore the safety and feasibility of continuous and intermittent hypoxia
therapy in PD and the differences of symptom modification of different hypoxia
protocols. Secondary outcomes include exploring the responsiveness of
subjective and objective motor outcome measures to assess the acute effects of
this intervention on PD symptoms, as well as elucidating mechanisms of
administering hypoxia relevant to PD.
Study design
Multiple randomized double-blinded N-of-1 trials (single patient cross-over
trial).
Intervention
Normobaric hypoxia will be delivered provided via an oxygen mask: one of the
following in OFF-condition: continuous hypoxia comparable to 2000m altitude
(16.3% O2) for 45 minutes, continuous hypoxia comparable to 4000m altitude
(12.7% O2) for 45 minutes, intermittent hypoxia for 45 minutes at 2000m,
intermittent hypoxia for 45 minutes at 4000m, continuous sea level conditions
(20.9% O2) for 45 minutes. 8 age-matched controls undergo the screening
intervention once.
Study burden and risks
Participants will visit our hospital 10 times across 10 consecutive weeks. Each
visit will commence in the morning with an estimated duration of 2.5 hours per
intervention day. Every participant will be screened for cardiorespiratory
comorbidities and if present, will be excluded. Induction of normobaric hypoxia
results in reduced oxygen availability for individuals living at sea level,
which typically does not lead to any physiological discomfort when applied at
the levels proposed in this study. Two senior physiologists on this project
have ample experience with both comparable and significantly more intense
hypoxia experiments.
However, it should be noted that experience in applying these techniques
specifically in Parkinson patients is limited. Therefore, during experiments,
vital parameters will be monitored continuously to monitor safety of the
intervention, and the use of clear cut-off values to terminate studies if
necessary.
Participants' benefit include adding to new insights into effect modifiers of
PD symptoms that might additionally provide insight into disease mechanisms.
For PD patients, these factors are important motivators for trial
participation.
Reinier Postlaan 4
Nijmegen 6525GC
NL
Reinier Postlaan 4
Nijmegen 6525GC
NL
Listed location countries
Age
Inclusion criteria
- Able to provide informed consent
- Age >18 years
- Clinical diagnosis of Parkinson*s disease by a movement disorder specialized
neurologist with Hoehn and Yahr staging 1.5 to 3.
- (for age-matched controls: all of the above, except for PD)
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
- Individuals with diseases leading to restrictive and obstructive pulmonary
diseases, pulmonary diffusion deficits, apnea and cardiac output deficits, such
as pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), sleep
apnea or excessive alcoholic intake, and congestive heart failure respectively.
- Arterial blood gas abnormalities at screening
- Individuals with shortness of breath or other airway or breathing-related
inconvenience related to lack of dopaminergic medication will be excluded.
- Inability to comply to intervention in off-medication condition (for example
due to extreme discomfort, distress or severe head tremor due to being OFF,
i.e. without dopaminergic medication).
- Individuals with unstable dopaminergic medication dose (changes in the last
month)
- Individuals likely to start dopaminergic treatment in the next month, also
judged by their treating neurologist
- Individuals with active deep brain stimulation
- Individuals unable to provide informed consent.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL77891.091.22 |