Menthol for Improving Movement and Sleep in Parkinson's Disease Patients

Taipei Medical University

Status and phase: Not yet enrolling; Phase 2

Conditions: Parkinson's Disease

Treatments: Drug: Menthol gloves and socks; Drug: Placebo gloves and socks

Study type: Interventional

Funder types: Other

Identifiers

NCT07294469

N202505079

Details and patient eligibility

About

Parkinson's disease (PD) is a progressive neurological disorder characterized by both motor and non-motor symptoms due to the degeneration of dopamine-producing neurons. There is currently no cure. Menthol, a natural compound that activates TRPM8 receptors, has shown neuroprotective and motor function benefits in preclinical PD models. In mice, distal limb immersion in menthol improved dopamine neuron survival and motor performance. Similar menthol-based interventions improved outcomes in a stroke model and a clinical trial with stroke patients. This study investigates whether topical menthol can offer therapeutic benefits for individuals with PD.

Full description

Parkinson's disease (PD) is a progressive neurological disorder that affects both motor and non-motor functions, with symptoms that can vary widely in severity. It is caused by the degeneration of dopamine-producing neurons in the substantia nigra, a brain region essential for movement control. The characteristic motor symptoms of PD include tremor, rigidity, bradykinesia, and postural instability. In addition to these motor impairments, many individuals with PD also experience non-motor symptoms, such as sleep disturbances, which can significantly impact their quality of life. Unfortunately, there is currently no cure for PD.

Menthol, a naturally occurring compound found in peppermint essential oil, has been shown to activate TRPM8 receptors in somatosensory neurons. Pharmacological activation of peripheral TRPM8 receptors enhances neural activity, which is subsequently transmitted to the brain.

In previous preclinical studies, the investigators used a dopamine toxin-induced PD mouse model and treated the mice with distal limb immersion in menthol. The results of immunohistochemical staining showed that limb immersion in menthol reduced the loss of dopamine neurons and increased the dopamine content in the mouse striatum. The mice's motor function also improved, as indicated by a significant increase in the time they spent running on the rotarod. The investigators also evaluated the effects of menthol in a stroke mouse model induced by MCAO. Topical application of menthol to the paw alleviated acute cerebral infarction and ischemia-induced sensorimotor deficits in MCAO mice.

In our recent clinical trial, the investigators evaluated the effects of menthol-containing gloves and socks in acute ischemic stroke patients. After four weeks of treatment, patients showed improvements in their Modified Rankin Scale (mRS) and Barthel Index (BI) scores, suggesting that this intervention may help enhance functional recovery. Based on these promising results, the investigators hypothesize that a similar approach could benefit individuals with PD.

The investigators aim to conduct a double-blind, randomized controlled trial evaluating the effectiveness of menthol-containing gloves and socks in treating motor deficits and sleep disorders in patients with PD：A total of 80 patients with PD will be randomized into the following groups: (1) menthol-containing gloves and socks (2) placebo. The treatment duration will be 4 weeks, with 4 weeks follow-up. All patients will be clinically assessed at the randomization, 4 and 8 week. Unified Parkinson's Disease Rating Scale (UPDRS) I,II,III, Pittsburgh Sleep Quality Index (PSQI), Parkinson's Disease Sleep Scale-2 (PDSS-2), Parkinson's Disease Questionnaire (PDQ-39) and detailed neurological examination will be included in the assessment.

Enrollment: 80 estimated patients

Sex: All

Ages: 30 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. aged between 30 and 80 years (inclusive);
2. diagnosed with idiopathic PD based on the Brain Bank criteria of the UK Parkinson's Disease Society less than 3 years;
3. Hoehn and Yahr stages 1-3 and currently receiving treatment; experiencing sleep disorders with a Pittsburgh Sleep Quality Index (PSQI) > 5;
4. has signed the informed consent form approved by the Institutional Review Board and dated accordingly;
5. no changes in PD medications within four weeks prior to participating in this trial, and no dosage changes during the study period;
6. able to use other medications that may affect sleep, except those explicitly prohibited, provided the dosage has been stable for the four weeks before screening and remains unchanged during the study.

Exclusion criteria

1. menthol allergy;
2. pregnant and breastfeeding women;
3. diagnosed with secondary and atypical PD;
4. patients with conditions such as uremia, cirrhosis, congestive heart failure with pulmonary edema, coagulation disorders, epilepsy, alcoholism, drug abuse, or
5. deemed unsuitable for participation in this study by the principal investigator.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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80 participants in 2 patient groups, including a placebo group

Menthol Group

Experimental group

Description:

Participants in this arm will wear gloves and socks containing menthol daily for four weeks.

Treatment:

Drug: Menthol gloves and socks

Placebo Group

Placebo Comparator group

Description:

Participants in this arm will wear placebo gloves and socks daily for four weeks. These are identical in appearance and material to those used in the treatment group but contain no active menthol compound.

Treatment:

Drug: Placebo gloves and socks