Clinical trial NCT06588972: Analgesic Effects of a Treatment With Cannabis Sativa Extract in Patients With Knee Osteoarthritis - CANOA (Cannabis for Osteoarthritis)
Official title: Analgesic Effects of a Treatment With Cannabis Sativa Extract in Patients With Knee Osteoarthritis - CANOA (Cannabis for Osteoarthritis)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: OSTEOARTHRITIS OF THE KNEE
Keywords: Osteoarthritis
Pain
Cannabinoids
Cannabinoid safety
Tetrahydrocannabinol
Cannabidiol
Lead sponsor: Federal University of Latin American Integration
Sponsor class: OTHER
First posted: 2024-09-19
Enrollment: 50
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Osteoarthritis (OA) is the most prevalent joint disease in humans, often causing disability in affected individuals, especially the elderly. OA is featured by mechanical articular pain, crackling and short post-immobilization stiffness. OA pain has variable pathophysiology, and despite many pharmacological options available, its treatment is often ineffective and presents significant side effects. On this way, the search for more effective and safer treatments is paramount on the OA field. Among potential treatments are the Cannabis-derived substances. Cannabis plants have been used for diverse purposes by mankind over thousands of years. Its best-known species, Cannabis sativa, has more than a hundred substances called cannabinoids, or more specifically phytocannabinoids, the most important of which are tetrahydrocannabinol (THC) and cannabidiol (CBD). These two phytocannabinoids display a number of pharmacological effects when used together or in isolation. Although many preclinical studies indicate usefulness of phytocannabinoids, currently the clinical evidence for its application is still scarce. Thus, this project aims to investigate the effects of an extract of Cannabis sativa rich in THC and CBD on pain of patients with knee OA, as well as the possible adverse events of this treatment.

Detailed description: Osteoarthritis (OA) is the most common osteoarticular pathology in humans. In Brazil, in 2004, its prevalence was estimated at 4.14% of the population , and is likely even higher today, given the country's accelerated aging and the increasing prevalence of obesity.

The pain of OA has variable pathophysiology, with nociceptive, inflammatory, and neuropathic mechanisms, along with central and peripheral sensitization, being the main cause of functional disability in patients.

Currently, the pharmacological therapeutic arsenal for treating OA pain includes non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and intra-articular corticosteroids. However, their use is associated with undesirable adverse effects, more common in the geriatric population, which is already exposed to polypharmacy. Due to the heterogeneity of pain pathophysiology in OA, no medication is fully effective in its control, and combinations of different classes of drugs with diverse mechanisms of action are generally employed, along with non-pharmacological measures such as patient education, rehabilitation, and, when necessary, surgical interventions .

Several studies demonstrate that cannabis has antiemetic, appetite-stimulating, analgesic, euphoric, anti-inflammatory, anticonvulsant, and sedative effects. Pain is the main cause of functional disability in patients affected by OA. Modulation of the endocannabinoid system through CB1 and CB2 receptor agonists, as well as FAAH inhibitors, has shown antinociceptive effects in animal models of OA induced by monosodium iodoacetate (MIA) , collagen , and adjuvants , as well as in models of natural OA in guinea pigs.

Other preclinical studies have shown potential effects of cannabinoids on OA progression, such as the inhibition of enzymes that produce local inflammatory mediators, such as nitric oxide and prostaglandin E2 , matrix metalloproteinases , and modulation of cortisol-mediated synovial fibroblast adhesion .

This will be a double-blind, randomized, placebo-controlled clinical trial. Patients who meet the inclusion criteria and agree to participate in the study will be randomized in a 1:1 ratio to three experimental groups, each with a sample size of 16 individuals, treated for 60 days as follows:

Group 1: placebo (Medium Chain Triglycerides solution, without any active principle); Group 2: C. sativa extract with a THC:CBD ratio of 1:10 (2mg:20mg/day); Group 3: C. sativa extract with a THC:CBD ratio of 1:10 (4mg:40mg/day). All patients selected for this study, if using any pharmacological or non-pharmacological therapy for OA, will have these therapies maintained throughout the clinical trial.

The experimental product acquired by LCP consists of a full spectrum extract of Cannabis sativa with a concentration of 20 mg/mL CBD and 2 mg/mL THC, diluted in the vehicle MCT (medium-chain triglycerides). All clinical evaluations will be conducted at three time points, T0, T30 and T60, while laboratory evaluations will be analyzed at T0 and T60.

Aim To evaluate the analgesic effect of a treatment with THC:CBD doses of a C. sativa extract in patients diagnosed with osteoarthritis.

Objectives:

To evaluate the analgesic effect of a THC:CBD treatment in C. sativa extract in patients diagnosed with osteoarthritis; To evaluate the anti-inflammatory effect of a THC:CBD treatment in C. sativa extract in patients diagnosed with osteoarthritis; To evaluate the symptomatic clinical safety profile of the treatment; To evaluate the renal, hepatic, and hemostatic safety profile of the treatment; To determine if there is an association between Lipoxin A4 levels and pain intensity levels in patients diagnosed with osteoarthritis.

Hypothesis:

The prescribed doses of THC:CBD/day induce analgesic and anti-inflammatory effects in patients diagnosed with osteoarthritis.

Eligibility criteria: Inclusion Criteria:

* Have a diagnosis of knee osteoarthritis, according to the ACR classification criteria (ALTMAN, 1986);
* Have a moderate or high level of pain induced by osteoarthritis (visual analog scale scale equal to or greater than 5);
* Voluntarily agree to take part in the study by signing the Informed Consent Form (ICF);
* For women of reproductive age, a negative Beta-HCG test, and use of a contraceptive method throughout the study.
* For women of reproductive age, a negative Beta-HCG test, and use of a contraceptive method throughout the study and 3 months after its conclusion.
* Age range of thirty (30) to seventy (70) years.

Exclusion Criteria:

* People with heart failure, hypertension or any heart disease;
* People with chronic kidney disease or liver failure;
* Patients with chronic inflammatory diseases;
* Patients with severe psychiatric illnesses, such as severe mood disorders and psychotic disorders;
* Current use of cannabinoids by any route of administration.
* Pregnant women
* Lactating women

Primary outcomes:
measure: Pain levels
timeFrame: 2 months
Secondary outcomes:
measure: Quality of life
timeFrame: 2 months
measure: Depression
timeFrame: 2 months
measure: Adverse events
timeFrame: 2 months
measure: Serious adverse events
timeFrame: 2 months
measure: Change in sleep quality
timeFrame: 2 months
measure: Biochemical markers
timeFrame: 2 months
measure: Molecular markers
timeFrame: 2 months
Other outcomes:
Locations:
city: Foz do Iguaçu
country: Brazil
facility: Federal University of Latin American Integration
state: Paraná
Study officials:
affiliation: Federal University of Latin American Integration
name: Francisney P Nascimento, 1
role: STUDY_DIRECTOR
References: