Safety and Effectiveness of Intermittent Hypoxia Treatment in Parkinson's Disease (TALISMAN-2)

A Randomized Phase 1b-2a Trial of the Safety and Effectiveness of Intermittent Hypoxia Treatment in Parkinson's Disease

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.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Other: Normoxia through hypoxic generator without active elements; Other: Hypoxia through modified hypoxic generator

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Radboud University Medical Center
  • Nijmegen, Netherlands, 6525EX
    • Dpt. of Physiology, Radboud University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Hypoxic generator without active elements, pulsewise ventilation assured to ascertain blinding	Other: Normoxia through hypoxic generator without active elements; Commercially available hypoxic generator, modified to allow for convenient remote interventions by non-expert participants, without active elements.
Experimental: Active intervention; FiO2 0.16 for 5 minutes interspersed with 5 minutes normoxia (intermittent hypoxia)	Other: Hypoxia through modified hypoxic generator; Commercially available hypoxic generator, modified to allow for convenient remote interventions by non-expert participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and nature of adverse events		2 months
Feasibility questionnaire, overall study success	Higher indicates better score	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MDS-UPDRS part II and III	Lower indicates better score	1 month
Purdue pegboard test (PPT)	Higher indicates better score	1 month
Timed up & Go Test (TUGT)	Lower indicates better score	1 month
Exercise tolerance (6-minute walk test, 6MWT)	Higher indicates better score	1 month
Accelerometry data for tremor amplitude	Lower indicates better score	1 month
Accelerometry data for pronation-supination	Higher indicates better score	1 month
Hematocrit	Higher indicates better result	1 month
Neurofilament light chain (NfL)	Higher indicates better result	1 month
BDNF	Higher indicates better result	1 month
Platelet-derived growth factor receptor beta (PDGFRβ)	Higher indicates better result	1 month
Clusterin	Higher indicates better result	1 month
GFAP	Higher indicates better result	1 month
UCH-L1	Higher indicates better result	1 month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parkinson's disease Questionnaire-39 (PDQ-39)	Lower indicates better score	1 month

Collaborators and Investigators

• Sponsor: Radboud University Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2023
• Primary Completion (Actual): August 30, 2024
• Study Completion (Actual): August 30, 2024

Study Registration Dates

• First Submitted: June 20, 2023
• First Submitted That Met QC Criteria: July 13, 2023
• First Posted (Actual): July 17, 2023

Study Record Updates

• Last Update Posted (Actual): August 11, 2025
• Last Update Submitted That Met QC Criteria: August 8, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Signs and Symptoms, Respiratory; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Hypoxia; Parkinson Disease
• Other Study ID Numbers: 114210

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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 publicly 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.
• IPD Sharing Time Frame: 1.5 years
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No