RELIEF-PD: Crisugabalin for Nociplastic Pain in Parkinson's Disease

Fficacy and Safety of Crisugabalin on Nociplastic Pain in Patients With Parkinson's Disease (RELIEF-PD): A Multicentre, Double-Blind, Randomised Controlled Trial

The goal of this clinical trial is to evaluate the efficacy and safety of Crisugabalin in adult participants with Parkinson's disease suffering from nociceptive pain. The main question it aims to answer is:

1. Does Crisugabalin significantly reduce pain intensity compared to placebo?
2. What is the safety and tolerability profile of Crisugabalin in patients with Parkinson's disease?

Researchers will compare participants receiving Crisugabalin to those receiving a matching placebo to see if the investigational drug leads to a greater reduction in pain scores and an improvement in quality of life without unacceptable side effects.

Participants will:

1. Be randomly assigned to receive either Crisugabalin capsules or a placebo.
2. Take the study medication orally twice daily for a specified treatment period.
3. Complete regular pain assessments using standardized scales (e.g., VAS or NRS).
4. Undergo physical examinations and laboratory tests to monitor safety.
5. Record any adverse events and changes in Parkinson's disease symptoms in a diary.

Eligibility Criteria

Inclusion Criteria:

1. Age 18-80 years (including 18 years), male or female.
2. Diagnosis of Parkinson's disease (PD) according to the diagnostic criteria established by the International Parkinson and Movement Disorder Society (MDS), including clinically established or clinically probable PD, with diagnosis made at least 6 months prior to screening.
3. Patients with nociplastic pain according to the classification of chronic pain in Parkinson's disease defined by the International Association for the Study of Pain (IASP).
4. Chronic pain associated with Parkinson's disease has been stable for at least 3 months prior to screening.
5. Stable anti-Parkinsonian medication regimen for at least 1 month prior to screening.
6. Average Daily Pain Score (ADPS) ≥4 during the week prior to screening.
7. Able to understand the study procedures and requirements, willing to comply with the clinical trial protocol, and voluntarily sign written informed consent.

Exclusion Criteria:

1. Severe Parkinson's disease defined as stage 5 on the Hoehn and Yahr Scale at screening (wheelchair-bound or bedridden unless aided).
2. Severe cognitive impairment or dementia defined as Mini-Mental State Examination (MMSE) score ≤24.
3. Presence of severe pain unrelated to Parkinson's disease.
4. Presence of neurological disorders unrelated to Parkinson's disease.
5. History of severe psychiatric disorders within 1 year prior to screening.
6. Presence of chronic systemic diseases that, in the investigator's opinion, may affect participation in the study, including but not limited to:

(1) Severe cardiopulmonary diseases, such as unstable angina, myocardial infarction, severe arrhythmia, heart failure classified as WHO functional class III-IV, poorly controlled hypertension despite treatment (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg at screening), or recurrent asthma attacks; (2) Neurological or psychiatric disorders including epilepsy, recurrent dizziness or headache, memory impairment, or cognitive disorders.

7. Severe hematologic, hepatic, or renal dysfunction meeting any of the following laboratory criteria:

1. Hematology: neutrophils <1.5 × 10⁹/L, or platelets <90 × 10⁹/L, or hemoglobin <100 g/L;
2. Liver function: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × the upper limit of normal (ULN), or total bilirubin (TBIL) >1.5 × ULN;
3. Renal function: estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² (calculated using the simplified MDRD equation) or patients receiving renal dialysis;
4. Creatine kinase (CK) >2 × ULN. 8. Use of crisugabalin, mirogabalin, pregabalin, or gabapentin within 28 days prior to screening, unless a washout period of at least 1 month has been completed.

9. Use of strong opioid medications for the treatment of Parkinson's disease-related pain within 3 months prior to screening.

10. Prior treatment with pregabalin ≥300 mg/day or gabapentin ≥1200 mg/day with lack of clinical efficacy, as judged by the investigator.

11. Known allergy or hypersensitivity to the investigational drug, rescue medication components, or other structurally related compounds or excipients.

12. Pregnant or breastfeeding women, women planning pregnancy during the study period, or participants unwilling to use reliable contraception from signing the informed consent form until 28 days after the last dose of the study drug (including condoms, spermicides, or intrauterine devices), or women planning to use progesterone-containing contraceptive pills during this period.

13. History of deep brain stimulation (DBS) surgery. 14. Participation in any other clinical trial within 30 days prior to screening.

15. Any other condition that, in the opinion of the investigator, makes the participant unsuitable for participation in this study.

Withdrawal Criteria:

1. Occurrence of serious adverse reactions that are intolerable to the participant.
2. Development of serious physical illness during the observation period.
3. Violation of the study protocol.
4. Loss to follow-up.