A randomized, double-blind, placebo-controlled 2-way crossover study to assess the analgesic effects of THC in patients with chronic neuropathic pain and to phenotype the responders to THC treatment.
- Trial ID
- 2022-502343-35-00
- Protocol
- CHDR2220
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to investigate the **analgesic effects** of THC 2% oil in patients with chronic neuropathic pain. Additionally, the study aims to explore the difference in these analgesic effects between phenotypical subgroups of patients, as defined by quantitative sensory testing (QST). This is clinically relevant as it may help tailor pain management strategies based on individual patient characteristics, potentially improving therapeutic outcomes.
Secondary objectives include:
- Evaluating the association between the analgesic effects of THC 2% oil and phenotypical characteristics of patients with neuropathic pain, using non-QST phenotyping tools.
- Assessing non-analgesic beneficial effects of THC 2% oil in patients with chronic neuropathic pain.
- Determining the safety and tolerability of THC 2% oil in this patient population.
Participants
The clinical trial focuses on evaluating the **analgesic effects** of THC 2% oil in individuals experiencing **chronic neuropathic pain**. The study population includes both male and female subjects aged 18 years or older. Participants are required to have a history of chronic neuropathic pain lasting at least three months, with a numeric rating scale score greater than 4. The trial encompasses a diverse range of neuropathic pain etiologies, including peripheral and central neuropathic pain syndromes, as well as complex regional pain syndrome type 2. Participants must also score 4 or higher on the Douleur Neuropathic 4 (DN4) questionnaire. The trial population is selected based on their ability to communicate effectively in Dutch and their willingness to adhere to study restrictions. The sponsor has not provided information regarding the total number of participants. The study includes a vulnerable population, ensuring a comprehensive understanding of the treatment's effects across different patient subgroups.
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, placebo-controlled** 2-way crossover study to evaluate the analgesic effects of **THC** in patients with **chronic neuropathic pain**. The trial aims to assess the difference in analgesic effects of THC 2% oil between phenotypical subgroups of patients as defined by quantitative sensory testing (QST). The study will involve the administration of **Clinican THC 2% oil** and a placebo, both delivered via **sublingual use**. The trial is expected to run from December 2022 to December 2025, with a maximum treatment period of 37 days for each participant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, presence of chronic neuropathic pain, and ability to communicate in Dutch. Following the screening, participants will be randomized to receive either the active treatment or placebo in a crossover manner. The primary endpoints include daily pain severity measured by a numeric rating scale (NRS) and weekly averages, while secondary endpoints encompass assessments of sleep quality, anxiety, depression, quality of life, and treatment-emergent adverse events.
Study visits will be scheduled throughout the trial to monitor vital signs, concomitant medication use, and any adverse events. The end-of-study visit will conclude the participant's involvement, with data collected on the final outcomes. Participants are expected to be involved for the duration of the treatment period, with conditions for early termination including withdrawal of consent or the occurrence of serious adverse events. The trial is conducted under the auspices of the Centre for Human Drug Research, ensuring adherence to ethical standards and scientific rigor.
Treatment
The clinical trial involves the administration of **Clinican THC 2% oil**, an experimental medication formulated as an oil for **sublingual use**. The active substance in this medication is **dronabinol**, a chemically derived compound. The maximum daily dose of Clinican THC 2% oil is 45 mg, with a total maximum dose of 1665 mg over a treatment period of 37 days. The administration schedule is designed to ensure consistent dosing, and participant compliance will be monitored throughout the trial to ensure adherence to the dosing regimen. The product is identified by the sponsor product code CHDR2220 and is authorized for use in this study by the Centre for Human Drug Research.
The study also includes a **placebo** comparator, referred to as the Placebo for Clinican THC 2% oil. This placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo is designed to mimic the appearance and administration route of the active treatment, although it contains no active pharmaceutical ingredients. The use of a placebo is critical in assessing the true analgesic effects of the active treatment by providing a baseline for comparison.
Efficacy
The efficacy of the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoints include the **Pain severity Numeric Rating Scale (NRS)**, which will be measured daily and averaged weekly, and the Experience Sampling Method (ESM) NRS pain scores. These measures will provide a comprehensive evaluation of the analgesic effects of THC 2% oil in patients with chronic neuropathic pain.
Secondary endpoints will further assess efficacy through various parameters, including sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) and daily Visual Analog Scale (VAS), anxiety and depression severity assessed by the Hospital Anxiety and Depression Scale (HADS), and quality of life evaluated using the SF36 questionnaire. Additional assessments include the Drug Effects Questionnaire (DEQ), which incorporates VAS measures for 'Feeling high', 'Drug liking', and 'Want more of the drug'. The trial will also utilize Trial At Home (T@H) geospatial and phone usage tracking, and monitor treatment-emergent (serious) adverse events ((S)AEs) and concomitant medication throughout the study at every visit. Vital signs, including pulse rate and blood pressure, will be recorded as per the assessment schedule.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed informed consent prior to any study-mandated procedure
- Male or female subjects aged 18 years or older, inclusive at screening.
- Presence of any chronic (at least 3 months) neuropathic pain with a numeric rating scale (NRS) > 4, disregarding etiology. Possible etiologies include, but are not restricted to: a. Peripheral neuropathic pain syndromes (e.g., painful (diabetic) polyneuropathy, , peripheral nerve injury pain, postamputation pain and persisting post-radiculopathy pain without evidence of current root compression); b. Central neuropathic pain syndromes (e.g., neuropathic pain associated with spinal injury, central poststroke pain, central neuropathic pain associated with multiple sclerosis); c. Complex regional pain syndrome type 2 (with evidence of nerve damage).
- Score of ≥4 on the Douleur Neuropathic 4 (DN4) questionnaire.
- Has the ability to communicate well with the Investigator in the Dutch language and willing to comply with the study restrictions.
Exclusion Criteria
- Evidence of any active or chronic disease or condition that is likely to interfere with, or for which the treatment is likely to interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator (following a detailed medical history, physical examination, vital signs (systolic and diastolic blood pressure, pulse rate, body temperature) and 12-lead electrocardiogram (ECG)). Deviations from the normal range may be accepted, if judged by the Investigator to have no clinical relevance.
- History of alcohol or substance use disorder or current use of more than 21 units of alcohol per week, or regular unprescribed use of sedatives, hypnotics, tranquilizers, or other addictive agents such as cocaine and non-prescribed amphetamines. The use of controlled substances, for example pain or sleep medication, will be allowed if prescribed by a registered physician. Documentation must be provided to confirm this.
- Current or recent (<4 weeks prior to screening) recreational or medicinal use of cannabis.
- Any known factor, condition, or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or current psychiatric disease.
- History of cannabis-induced psychosis, schizophrenia or other clinically relevant psychiatric disorders, as judged by the investigator.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 The Netherlands | Recruiting | 01 Dec 2022 | — |
| Netherlands | — | — | 200 |
Sites & Investigators
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo for Clinican THC 2% oil | Placebo | N/A | — | — | — | N/A |
Clinican THC 2% oil | Test | OIL | SUBLINGUAL USE | 45 | 37 | PRD9986891 |