Clinical trial NCT05948761: Safety and Effectiveness of Intermittent Hypoxia Treatment in Parkinson's Disease
Official title: A Randomized Phase 1b-2a Trial of the Safety and Effectiveness of Intermittent Hypoxia Treatment in Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Parkinson Disease
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2023-07-17
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To explore the safety, feasibility and net symptomatic effects of multiple (3x/week, for 4 weeks) intermittent hypoxia treatment sessions in individuals with PD. Secondary outcomes include exploring induction of relevant neuroprotective pathways as measured in serum.

Detailed description: Intermittent hypoxia therapy is a non-pharmacological intervention used by athletes and individuals with cardiovascular disease, amongst others. The safety and feasibility of (intermittent) hypoxia therapy and its short-term effects on Parkinson's disease (PD) symptoms were assessed in a previous exploratory phase I trial. However, the net effects of multiple hypoxia treatment sessions on PD symptoms are unknown. The results of the previous phase I trial informed the study design of the newly proposed phase 1b-2a safety and efficacy trial.

45 minutes of normobaric intermittent hypoxia (FiO2 0.16 for 5 minutes interspersed with 5 minutes normoxia) will be delivered via a hypoxicator (a device that titrates decreased fractional oxygen from room air) through an oxygen mask in the hospital and subsequently at participants' homes. Interventions will be conducted 3 times a week, for 4 weeks in total.

Eligibility criteria: Inclusion criteria

* Informed consent
* Clinical diagnosis of Parkinson's disease by a movement disorder specialized neurologist.
* Hoehn and Yahr staging 1 to and including 3 (indicating mild to moderate 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, sleep apnea and cardiac output deficits, such as pulmonary fibrosis, COPD, sleep apnea or excessive alcoholic intake, and congestive heart failure respectively
* Individuals with coronary artery disease NYHA classes III and IV
* Arterial blood gas abnormalities at screening procedure
* Individuals with shortness of breath or other airway or breathing-related inconvenience related to lack of dopaminergic medication
* Inability for in-clinic measurements in OFF phase
* Individuals with active deep brain stimulation

Primary outcomes:
measure: Number and nature of adverse events
timeFrame: 2 months
measure: Feasibility questionnaire, overall study success
timeFrame: 1 month
Secondary outcomes:
measure: MDS-UPDRS part II and III
timeFrame: 1 month
measure: Purdue pegboard test (PPT)
timeFrame: 1 month
measure: Timed up & Go Test (TUGT)
timeFrame: 1 month
measure: Exercise tolerance (6-minute walk test, 6MWT)
timeFrame: 1 month
measure: Accelerometry data for tremor amplitude
timeFrame: 1 month
measure: Accelerometry data for pronation-supination
timeFrame: 1 month
measure: Hematocrit
timeFrame: 1 month
measure: Neurofilament light chain (NfL)
timeFrame: 1 month
measure: BDNF
timeFrame: 1 month
measure: Platelet-derived growth factor receptor beta (PDGFRβ)
timeFrame: 1 month
measure: Clusterin
timeFrame: 1 month
measure: GFAP
timeFrame: 1 month
measure: UCH-L1
timeFrame: 1 month
Other outcomes:
measure: Parkinson's disease Questionnaire-39 (PDQ-39)
timeFrame: 1 month
Locations:
city: Nijmegen
country: Netherlands
facility: Dpt. of Physiology, Radboud University Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
Study officials:
References:
citation: Janssen 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.