Parkinson DiseasePhase 1/2TALISMANNCT05214287
Multiple N-of-1 Trials of (Intermittent) Hypoxia Therapy in Parkinson's Disease
A Phase 1/2 study testing Hypoxic Gas Mixture in people with Parkinson Disease and Effect of Drug, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
In recent years, mitochondrial dysfunction and oxidative stress have been implicated in PD pathophysiology. Intermittent hypoxia therapy (IHT) is an upcoming treatment used by elite athletes as well as fragile individuals in clinical settings that works by improving exercise tolerance, neuroplasticity and inducing… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Parkinson Disease, Effect of Drug
- What is being tested?
- Hypoxic Gas Mixture
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 1 siteNetherlands
- Study dates
- 22 Feb 2022to 12 Jul 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent
- Clinical diagnosis of Parkinson's disease by a movement disorder specialized neurologist with Hoehn and Yahr staging 1.5 to 3.
- 15 individuals with self-reported personal experience of positive altitude effect.
- 5 individuals without self-reported personal experience of positive altitude effect.
Who cannot join
- Individuals with diseases leading to restrictive and obstructive pulmonary diseases, pulmonary diffusion deficits, apnea and cardiac output deficits, such as pulmonary fibrosis, COPD, sleep apnea or excessive alcoholic intake, and congestive heart failure respectively.
- Arterial blood gas abnormalities at screening day (as per normal limits)
- 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.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Dpt. of Physiology, Radboud University Medical Center
Nijmegen, 6525EX
About this study
Official title: An N-of-1 Double-blind Randomized Phase 1 Trial of the Safety and Feasibility of (Intermittent) Hypoxia Therapy in Parkinson's Disease (TALISMAN)
In recent years, mitochondrial dysfunction and oxidative stress have been implicated in PD pathophysiology. Intermittent hypoxia therapy (IHT) is an upcoming treatment used by elite athletes as well as fragile individuals in clinical settings that works by improving exercise tolerance, neuroplasticity and inducing hypoxic preconditioning (HPC). HPC might improve the oxidative stress response in PD on the long-term. In addition, preclinical evidence suggests beneficial short-term effects such as influence on dopamine and noradrenalin release. Anecdotal evidence indeed suggests that visiting high-altitude areas improves PD symptoms and it is hypothesized that this effect results from decreased oxygen pressure at high altitudes. The safety and feasibility of (intermittent) hypoxia therapy on PD symptoms will be assessed in an exploratory phase I randomized-controlled trial.
Read the detailed description
Parkinson's disease (PD) currently affects 10 million people worldwide and its prevalence is projected to exponentially rise further in the absence of disease-modifying therapies. A scarcity of symptomatic treatments is available and the mainstay of therapy has been levodopa for over half a century. Although this treatment suffices for many patients in early phases of PD, treatment burden is significant, as are the adverse effects, wearing-off and dyskinesia that develop with disease progression. Therefore, additional treatment modalities are needed.
Preclinical studies have suggested that moderate hypoxia provokes release of survival-enhancing neurotransmitters, such as dopamine release from the substantia nigra. Clinical and preclinical evidence suggests the effects of hypoxia seem especially robust when applied using intermittent hypoxia therapy (IHT) compared to continuous hypoxia. IHT means that hypoxia is present for relatively short periods (i.e. minutes), interspersed with short periods of recovery at normoxia (i.e. sea-level). The precise working mechanism of IHT on the short term remains unclear, but the immediate clinical effects appear to be related to augmented dopamine release from the substantia nigra. Specifically, IHT may improve parkinsonian symptoms via activation of the Hypoxia Inducible Factor 1 (HIF-1) pathway, which in turn activates tyrosine hydroxylase (TH), which is the main rate-limiting enzyme in the production of dopamine. Several studies have demonstrated that HIF-1 stabilization leads to an increase in TH production, and consequently a rise in cellular dopamine content. IHT is a therapy proven safe and effective in a variety of disciplines, including fragile populations such as individuals with chronic obstructive pulmonary disorder (COPD), cardiac morbidity and spinal cord injury. Long-term application of IHT protocols was associated with improved oxidative stress response and adaptive plasticity in the dopaminergic system of rodents, suggesting that in addition to the acute symptomatic effects, repeated exposure to (intermittent) hypoxia might also exert some long-term neuroprotective effects. The general concept behind a possible (long-term) neuroprotective effect of IHT is the phenomenon of hypoxic conditioning: induction of a sub-toxic hypoxic stimulus to improve the (systemic) tolerance of cells and tissues to subsequent more severe stimuli, either in dose or duration. In this way, key adaptive mechanisms are induced that allow maintenance of cellular homeostasis under low-oxygen conditions. Among these adaptive mechanisms, activation of HIF-1 is the most prominent and most extensively described mechanism. Interestingly, IHT protocols also blocked the neurotoxic effect of agents that induce PD in rodents, preventing development of locomotor deficits, again suggesting some neuroprotective effects. Furthermore, circumstantial anecdotal evidence from individuals with PD suggests that ascending to high-altitude areas (e.g. on holidays) improves motor symptoms of PD, which the investigators recently confirmed in a survey conducted in the holiday context (https://doi.org/10.1002/mdc3.13597). The investigators hypothesize that the positive effect of altitude on the symptoms of PD result from decreased oxygen pressure at high altitude, which serves as an acute bodily stressor that releases survival-enhancing neurotransmitters such as dopamine and noradrenaline and might induce neuroprotective mechanisms.
The investigators will assess the potential of IHT in PD by assessing symptomatic effects of intermittent hypoxia therapy in an exploratory phase I trial. Primary objectives are the safety and feasibility of intermittent hypoxia in PD and assessing the responsiveness of subjective and standardized symptom scales to this intervention. This trial will exploit an aggregated N-of-1 approach, which allows testing multiple high-altitude simulation protocols and outcome measures, analysis of the treatment effect in individuals as it can account for random variation for treatment effects in the individual and enhances methodological power due to repeated treatment pairs.
During a screening procedure, participants undergo pulmonary function testing, carbon monoxide diffusion capacity testing and electrocardiography. If no cardiorespiratory abnormalities are demonstrated, individuals undergo a hypoxic intervention with gradually decreasing FiO2 levels from room air to either FiO2 0.127 or an arterial oxygen saturation (SaO2) of 80%, under vital parameter and blood gas monitoring. If a participant reaches FiO2 0.127 without SaO2 <80%, the most intense active interventions will contain that FiO2. If a participant has an SaO2 <80% before FiO2 0.127 is reached but still has an SaO2 of 80% or higher at FiO2 0.133, the most intense active intervention will be FiO2 0.133 instead of 0.127 (see Interventions)
- Conditions
- Parkinson Disease, Effect of Drug
- Being tested
- Hypoxic Gas Mixture
- Keywords
- Parkinson's disease, Treatment, Intermittent hypoxia therapy, IHT, Disease-modifying treatment, Symptomatic therapy, Neurodegenerative Diseases, Synucleinopathies, Oxygen Deficiency, Hypoxia, Brain, Movement Disorders
- Medical subject headings
- Parkinson Disease, Neurodegenerative Diseases, Synucleinopathies, Hypoxia, Hypoxia, Brain, Movement Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypoxic Gas MixtureDrug
Also called Hypoxicator
Using a commercially available hypoxicator, varying gas mixtures as described will be administered via a tight-fitting oxygen mask. In the circuitry, a three-way valve is placed that allows for the intermittent administration of hypoxia: the valve either passes the hypoxic mixture from the hypoxicator or room air.
| Study group | Role | What they receive |
|---|---|---|
| Intermittent with 5x5-minutes, FiO2 0.163 | Experimental | Delivered intermittently, with FiO2 0.163 and room-air, each 5 minutes, for 5 cycles/session Receives: Drug: Hypoxic Gas Mixture |
| Intermittent with 5x5-minutes, FiO2 0.127 or 0.133 | Experimental | Delivered intermittently, with FiO2 0.127 or 0.133 (depending on SaO2 during screening procedure at FiO2 0.127, see study procedures) and room-air, each 5 minutes, for 5 cycles/session Receives: Drug: Hypoxic Gas Mixture |
| Continuous for 45 minutes, FiO2 0.163 | Experimental | Delivered via the hypoxicator Receives: Drug: Hypoxic Gas Mixture |
| Continuous for 45 minutes, FiO2 0.127 or 0.133 | Experimental | FiO2 0.127 or 0.133 (depending on SaO2 during screening procedure at FiO2 0.127, see study procedures) Receives: Drug: Hypoxic Gas Mixture |
| Continuous for 45 minutes, FiO2 0.209 | Placebo comparator | Delivered via an open three-way valve in the circuitry from hypoxicator to the participant Receives: Drug: Hypoxic Gas Mixture |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nature and number of adverse events
Actively reported during intervention and passively for up to 3 days after the intervention, adverse events will be collected.
Measured: Until 3 days post-intervention
Self-reported dizziness, discomfort and stress on a ten-point scale
Every 10 minutes up to one hour post-intervention, one time next morning post-intervention, 10-point Likert scale, lower is better.
Measured: Until 3 days post-intervention
Blood pressure
Systolic and diastolic blood pressure
Measured: Baseline and every 5 mins until 30 mins post-intervention
Heartrate
Beats/min
Measured: Baseline and every 5 mins until 30 mins post-intervention
Respiratory rate
Breaths/min
Measured: Baseline and every 5 mins until 30 mins post-intervention
Oxygen saturation
Percentage
Measured: Baseline and every 5 mins until 30 mins post-intervention
Feasibility questionnaire
17-item scale, scored 1-10, lower is better. Subscores and total score
Measured: After 1st, 5th, 10th post-intervention test
Secondary outcomes (11)
Participant-selected motor symptom
Change from (pre-treatment) baseline in the symptom that improved most during previous positive altitude effect (if applicable), or other symptom of choice. Self-reported severity scores on a Likert-scale. 10-point Likert scale allowing half points. Lower is better.
Measured: Directly after, as well as 30 and 60 minutes after the intervention and four times once every hour after that. In addition, these will be measured once every morning (i.e. in OFF) for the next three mornings after the intervention.
General impression of PD symptoms
Change from (pre-treatment) baseline on 10-point Likert scale allowing half points. Lower is better.
Measured: Directly after, as well as 30 and 60 minutes after the intervention and four times once every hour after that. In addition, these will be measured once every morning (i.e. in OFF) for the next three mornings after the intervention.
Urge to take dopaminergic medication
Change from (pre-treatment) baseline on 10-point Likert scale allowing half points. Lower is better.
Measured: Directly after, as well as 30 and 60 minutes after the intervention and four times once every hour after that. In addition, these will be measured once every morning (i.e. in OFF) for the next three mornings after the intervention.
Timed Up & Go Test
Change from (pre-treatment) baseline in total time and steps. The Timed Up \& Go Test is a test that evaluates primarily gait functioning. Lower is better.
Measured: 30 minutes
MiniBESTest
Change from (pre-treatment) baseline in item subscores and total score. The MiniBESTest is a concise balance test. Higher is better.
Measured: 30 minutes
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III
The MDS-UPDRS part III is the gold standard for motor assessment in Parkinson's disease. Change form (pre-treatment) baseline in item subscores and total scores. Lower is better.
Measured: 30 minutes
Finger tapping
Change from (pre-treatment) baseline in number of taps during 10-second trials on both hands, one session each. Finger tapping is considered a measure of bradykinesia. Higher is better.
Measured: 30 minutes
MDS Non-Motor Symptoms Scale (only items related to stress, fatigue, mood, anxiety, pain)
The most important potentially adaptive non-motor symptoms mentioned in this gold standard for non-motor symptom screening are selected. Likert scale 1-10 (allowing half points). Change from (pre-treatment) baseline. Lower is better.
Measured: 30 minutes
Accelerometry during MDS-UPDRS part III, items on pronation-supination and tremor
During the MDS-UPDRS part III, accelerometry allows for quantification of therapeutic effects in addition to the MDS-UPDRS part III. Lower amplitude is better in tremor, higher frequency and rotational power is better in pronation-supination. Change from (pre-treatment) baseline.
Measured: 30 minutes
Heart Rate Variability (HRV)
Average HRV during intervention and post intervention. HRV is a marker of cardiovascular stress. Change form (pre-treatment) baseline. Lower equals more stress.
Measured: 30 minutes
Modified Purdue pegboard test
Change from (pre-treatment) baseline in number of pins per side. The Purdue pegboard test is primarily a measure of bradykinesia, hypokinesia and fine motor skills. Higher is better.
Measured: 30 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2022
- Study start22 Feb 2022
- Primary completion12 Jul 2023
- Study completion12 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- The investigators will deploy an N-of-1 trial design (also known as single participant cross-over trial) in which multiple treatment pairs of active treatment and placebo are offered to an individual participant in a randomized, double-blind fashion. In an N-of-1 trial, random variation within the treatment effect at the individual level can be better accounted for and methodological power is optimized due to repeated treatment-pairs and the fact that the individual participant acts as their own control. Thanks to this design, in which each treatment-pair should be exchangeable in time, N-of-1 trials are especially suitable to investigate treatments in chronic, symptomatic conditions, where period effects (i.e. changes in disease state) and carry over effects (i.e. lingering hypoxia effects) are small. Given the slowly progressive nature of PD with relative stable symptoms, several N-of-1 trials have already been successfully performed to study symptomatic treatments in PD.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Michael J. Fox Foundation for Parkinson's Research
- Responsible party
- Sponsor
- Investigators
- prof. dr. Bastiaan R. Bloem, Principal investigator, Center of Expertise for Parkinson and Movement Disorders, Radboud university medical centerprof. dr. Dick H.J. Thijssen, Principal investigator, Department of Integrative Physiology, Radboud university medical center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05214287
- Sponsor's protocol ID
- 112203
- Other IDs
- NL.77891.091.21, 2021-005480-41, 2021-12410
- Acronym
- TALISMAN
- Status last verified
- Jun 2023
- First submitted
- 28 Dec 2021
- Last updated
- 21 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized data will be shared with The Michael J. Fox Foundation for Parkinson's Research (the study funder). This data may be kept for storage at a central repository either hosted by The Michael J. Fox Foundation, its collaborators, or consultants and will be kept indefinitely. Anonymized data will be made publically available for the intended use of research in Parkinson's disease as well as other biomedical research studies that may not be related to Parkinson's disease.
Publications
Janssen Daalen JM, Straatsma IR, van Hees JWH, Weevers A, van de Wetering-van Dongen VA, Nijkrake MJ, Meinders MJ, Bosch FH, Kox M, Ainslie PN, Bloem BR, Thijssen DHJ. Respiratory Dysfunction and Abnormal Hypoxic Ventilatory Response in Mild to Moderate Parkinson's Disease. Mov Disord Clin Pract. 2024 Dec;11(12):1550-1558. doi: 10.1002/mdc3.14249. Epub 2024 Nov 5.
PubMed 39498807Janssen Daalen JM, Meinders MJ, Giardina F, Roes KCB, Stunnenberg BC, Mathur S, Ainslie PN, Thijssen DHJ, Bloem BR. Multiple N-of-1 trials to investigate hypoxia therapy in Parkinson's disease: study rationale and protocol. BMC Neurol. 2022 Jul 14;22(1):262. doi: 10.1186/s12883-022-02770-7.
PubMed 35836147
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An N-of-1 Double-blind Randomized Phase 1 Trial of the Safety and Feasibility of (Intermittent) Hypoxia Therapy in Parkinson's Disease (TALISMAN)
- ClinicalTrials.gov ID
- NCT05214287
- Acronym / sponsor ID
- TALISMAN / 112203
- Conditions
- Parkinson Disease, Effect of Drug
- Keywords
- Parkinson's disease, Treatment, Intermittent hypoxia therapy, IHT, Disease-modifying treatment, Symptomatic therapy, Neurodegenerative Diseases, Synucleinopathies
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Michael J. Fox Foundation for Parkinson's Research
- Study start
- 22 Feb 2022 (actual)
- Primary completion
- 12 Jul 2023 (actual)
- Study completion
- 12 Jul 2023 (actual)
- First posted
- 28 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In recent years, mitochondrial dysfunction and oxidative stress have been implicated in PD pathophysiology. Intermittent hypoxia therapy (IHT) is an upcoming treatment used by elite athletes as well as fragile individuals in clinical settings that works by improving exercise tolerance, neuroplasticity and inducing hypoxic preconditioning (HPC). HPC might improve the oxidative stress response in PD on the long-term. In addition, preclinical evidence suggests beneficial short-term effects such as influence on dopamine and noradrenalin release. Anecdotal evidence indeed suggests that visiting high-altitude areas improves PD symptoms and it is hypothesized that this effect results from decreased oxygen pressure at high altitudes. The safety and feasibility of (intermittent) hypoxia therapy on PD symptoms will be assessed in an exploratory phase I randomized-controlled trial.
Detailed description
Parkinson's disease (PD) currently affects 10 million people worldwide and its prevalence is projected to exponentially rise further in the absence of disease-modifying therapies. A scarcity of symptomatic treatments is available and the mainstay of therapy has been levodopa for over half a century. Although this treatment suffices for many patients in early phases of PD, treatment burden is significant, as are the adverse effects, wearing-off and dyskinesia that develop with disease progression. Therefore, additional treatment modalities are needed.
Preclinical studies have suggested that moderate hypoxia provokes release of survival-enhancing neurotransmitters, such as dopamine release from the substantia nigra. Clinical and preclinical evidence suggests the effects of hypoxia seem especially robust when applied using intermittent hypoxia therapy (IHT) compared to continuous hypoxia. IHT means that hypoxia is present for relatively short periods (i.e. minutes), interspersed with short periods of recovery at normoxia (i.e. sea-level). The precise working mechanism of IHT on the short term remains unclear, but the immediate clinical effects appear to be related to augmented dopamine release from the substantia nigra. Specifically, IHT may improve parkinsonian symptoms via activation of the Hypoxia Inducible Factor 1 (HIF-1) pathway, which in turn activates tyrosine hydroxylase (TH), which is the main rate-limiting enzyme in the production of dopamine. Several studies have demonstrated that HIF-1 stabilization leads to an increase in TH production, and consequently a rise in cellular dopamine content. IHT is a therapy proven safe and effective in a variety of disciplines, including fragile populations such as individuals with chronic obstructive pulmonary disorder (COPD), cardiac morbidity and spinal cord injury. Long-term application of IHT protocols was associated with improved oxidative stress response and adaptive plasticity in the dopaminergic system of rodents, suggesting that in addition to the acute symptomatic effects, repeated exposure to (intermittent) hypoxia might also exert some long-term neuroprotective effects. The general concept behind a possible (long-term) neuroprotective effect of IHT is the phenomenon of hypoxic conditioning: induction of a sub-toxic hypoxic stimulus to improve the (systemic) tolerance of cells and tissues to subsequent more severe stimuli, either in dose or duration. In this way, key adaptive mechanisms are induced that allow maintenance of cellular homeostasis under low-oxygen conditions. Among these adaptive mechanisms, activation of HIF-1 is the most prominent and most extensively described mechanism. Interestingly, IHT protocols also blocked the neurotoxic effect of agents that induce PD in rodents, preventing development of locomotor deficits, again suggesting some neuroprotective effects. Furthermore, circumstantial anecdotal evidence from individuals with PD suggests that ascending to high-altitude areas (e.g. on holidays) improves motor symptoms of PD, which the investigators recently confirmed in a survey conducted in the holiday context (https://doi.org/10.1002/mdc3.13597). The investigators hypothesize that the positive effect of altitude on the symptoms of PD result from decreased oxygen pressure at high altitude, which serves as an acute bodily stressor that releases survival-enhancing neurotransmitters such as dopamine and noradrenaline and might induce neuroprotective mechanisms.
The investigators will assess the potential of IHT in PD by assessing symptomatic effects of intermittent hypoxia therapy in an exploratory phase I trial. Primary objectives are the safety and feasibility of intermittent hypoxia in PD and assessing the responsiveness of subjective and standardized symptom scales to this intervention. This trial will exploit an aggregated N-of-1 approach, which allows testing multiple high-altitude simulation protocols and outcome measures, analysis of the treatment effect in individuals as it can account for random variation for treatment effects in the individual and enhances methodological power due to repeated treatment pairs.
During a screening procedure, participants undergo pulmonary function testing, carbon monoxide diffusion capacity testing and electrocardiography. If no cardiorespiratory abnormalities are demonstrated, individuals undergo a hypoxic intervention with gradually decreasing FiO2 levels from room air to either FiO2 0.127 or an arterial oxygen saturation (SaO2) of 80%, under vital parameter and blood gas monitoring. If a participant reaches FiO2 0.127 without SaO2 <80%, the most intense active interventions will contain that FiO2. If a participant has an SaO2 <80% before FiO2 0.127 is reached but still has an SaO2 of 80% or higher at FiO2 0.133, the most intense active intervention will be FiO2 0.133 instead of 0.127 (see Interventions)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 5
- Model description
- The investigators will deploy an N-of-1 trial design (also known as single participant cross-over trial) in which multiple treatment pairs of active treatment and placebo are offered to an individual participant in a randomized, double-blind fashion. In an N-of-1 trial, random variation within the treatment effect at the individual level can be better accounted for and methodological power is optimized due to repeated treatment-pairs and the fact that the individual participant acts as their own control. Thanks to this design, in which each treatment-pair should be exchangeable in time, N-of-1 trials are especially suitable to investigate treatments in chronic, symptomatic conditions, where period effects (i.e. changes in disease state) and carry over effects (i.e. lingering hypoxia effects) are small. Given the slowly progressive nature of PD with relative stable symptoms, several N-of-1 trials have already been successfully performed to study symptomatic treatments in PD.
| Arm | Type | Receives |
|---|---|---|
| Intermittent with 5x5-minutes, FiO2 0.163 | Experimental | Drug: Hypoxic Gas MixtureDelivered intermittently, with FiO2 0.163 and room-air, each 5 minutes, for 5 cycles/session |
| Intermittent with 5x5-minutes, FiO2 0.127 or 0.133 | Experimental | Drug: Hypoxic Gas MixtureDelivered intermittently, with FiO2 0.127 or 0.133 (depending on SaO2 during screening procedure at FiO2 0.127, see study procedures) and room-air, each 5 minutes, for 5 cycles/session |
| Continuous for 45 minutes, FiO2 0.163 | Experimental | Drug: Hypoxic Gas MixtureDelivered via the hypoxicator |
| Continuous for 45 minutes, FiO2 0.127 or 0.133 | Experimental | Drug: Hypoxic Gas MixtureFiO2 0.127 or 0.133 (depending on SaO2 during screening procedure at FiO2 0.127, see study procedures) |
| Continuous for 45 minutes, FiO2 0.209 | Placebo comparator | Drug: Hypoxic Gas MixtureDelivered via an open three-way valve in the circuitry from hypoxicator to the participant |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Informed consent
- Clinical diagnosis of Parkinson's disease by a movement disorder specialized neurologist with Hoehn and Yahr staging 1.5 to 3.
- 15 individuals with self-reported personal experience of positive altitude effect.
- 5 individuals without self-reported personal experience of positive altitude effect.
Key exclusion criteria (8 listed)
- Individuals with diseases leading to restrictive and obstructive pulmonary diseases, pulmonary diffusion deficits, apnea and cardiac output deficits, such as pulmonary fibrosis, COPD, sleep apnea or excessive alcoholic intake, and congestive heart failure respectively.
- Arterial blood gas abnormalities at screening day (as per normal limits)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hypoxic Gas MixtureAlso: HypoxicatorUsing a commercially available hypoxicator, varying gas mixtures as described will be administered via a tight-fitting oxygen mask. In the circuitry, a three-way valve is placed that allows for the intermittent administration of hypoxia: the valve either passes the hypoxic mixture from the hypoxicator or room air. | Drug | Continuous for 45 minutes, FiO2 0.127 or 0.133, Continuous for 45 minutes, FiO2 0.163, Continuous for 45 minutes, FiO2 0.209, Intermittent with 5x5-minutes, FiO2 0.127 or 0.133, Intermittent with 5x5-minutes, FiO2 0.163 |
Primary outcome
Nature and number of adverse events
Time frame: Until 3 days post-intervention
Actively reported during intervention and passively for up to 3 days after the intervention, adverse events will be collected.
Self-reported dizziness, discomfort and stress on a ten-point scale
Time frame: Until 3 days post-intervention
Every 10 minutes up to one hour post-intervention, one time next morning post-intervention, 10-point Likert scale, lower is better.
Blood pressure
Time frame: Baseline and every 5 mins until 30 mins post-intervention
Systolic and diastolic blood pressure
Heartrate
Time frame: Baseline and every 5 mins until 30 mins post-intervention
Beats/min
Respiratory rate
Time frame: Baseline and every 5 mins until 30 mins post-intervention
Breaths/min
Oxygen saturation
Time frame: Baseline and every 5 mins until 30 mins post-intervention
Percentage
Feasibility questionnaire
Time frame: After 1st, 5th, 10th post-intervention test
17-item scale, scored 1-10, lower is better. Subscores and total score
11 secondary outcomes
Participant-selected motor symptom
Time frame: Directly after, as well as 30 and 60 minutes after the intervention and four times once every hour after that. In addition, these will be measured once every morning (i.e. in OFF) for the next three mornings after the intervention.
General impression of PD symptoms
Time frame: Directly after, as well as 30 and 60 minutes after the intervention and four times once every hour after that. In addition, these will be measured once every morning (i.e. in OFF) for the next three mornings after the intervention.
Urge to take dopaminergic medication
Time frame: Directly after, as well as 30 and 60 minutes after the intervention and four times once every hour after that. In addition, these will be measured once every morning (i.e. in OFF) for the next three mornings after the intervention.
Timed Up & Go Test
Time frame: 30 minutes
MiniBESTest
Time frame: 30 minutes
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III
Time frame: 30 minutes
Finger tapping
Time frame: 30 minutes
MDS Non-Motor Symptoms Scale (only items related to stress, fatigue, mood, anxiety, pain)
Time frame: 30 minutes
Accelerometry during MDS-UPDRS part III, items on pronation-supination and tremor
Time frame: 30 minutes
Heart Rate Variability (HRV)
Time frame: 30 minutes
Modified Purdue pegboard test
Time frame: 30 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2023.
- Derived from this study: PubMed 39498807Janssen Daalen JM, Straatsma IR, van Hees JWH, Weevers A, van de Wetering-van Dongen VA, Nijkrake MJ, Meinders MJ, Bosch FH, Kox M, Ainslie PN, Bloem BR, Thijssen DHJ. Respiratory Dysfunction and Abnormal Hypoxic Ventilatory Response in Mild to Moderate Parkinson's Disease. Mov Disord Clin Pract. 2024 Dec;11(12):1550-1558. doi: 10.1002/mdc3.14249. Epub 2024 Nov 5.
- Derived from this study: PubMed 35836147Janssen Daalen JM, Meinders MJ, Giardina F, Roes KCB, Stunnenberg BC, Mathur S, Ainslie PN, Thijssen DHJ, Bloem BR. Multiple N-of-1 trials to investigate hypoxia therapy in Parkinson's disease: study rationale and protocol. BMC Neurol. 2022 Jul 14;22(1):262. doi: 10.1186/s12883-022-02770-7.
- Individual participant dataSharing planned: Yes. Anonymized data will be shared with The Michael J. Fox Foundation for Parkinson's Research (the study funder). This data may be kept for storage at a central repository either hosted by The Michael J. Fox Foundation, its collaborators, or consultants and will be kept indefinitely. Anonymized data will be made publically available for the intended use of research in Parkinson's disease as well as other biomedical research studies that may not be related to Parkinson's disease.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
prof. dr. Bastiaan R. Bloem principal investigator
Center of Expertise for Parkinson and Movement Disorders, Radboud university medical center
prof. dr. Dick H.J. Thijssen principal investigator
Department of Integrative Physiology, Radboud university medical center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Hypoxic Gas Mixture in people with Parkinson Disease and Effect of Drug, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Nature and number of adverse events (time frame: Until 3 days post-intervention). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05214287, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2023.