CBD/THC Solution as a Pharmacological Strategy for Patients With Fibromyalgia. Single-center, Double-blind, Randomized, Placebo-controlled Clinical Trial Protocol (FibroCann)
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 40
- 主要终点
- Dose-response curve and median effective dose
研究概览
简要总结
Fibromyalgia is considered a chronic pain syndrome, non-inflammatory, of unknown etiology, which manifests itself in the musculoskeletal system in up to 2.5% of the general population, predominantly in females, mainly between 35 and 44 years old, having a direct impact on the quality of life of their patients (JUNIOR; GOLDENFUM; SIENA, 2012; HEYMANN et al., 2017). In 1990, eighteen (18) specific sites were defined as tender points which are used to better diagnose fibromyalgia (WOLFE et al., 2010). Due to its clinical and exclusion diagnosis, treatment usually starts late, which allows the progression of symptoms and corroborates its low efficiency in the long term (DE SOUSA BRAZ et al., 2011). Due to the ineffective results and significant side effects that conventional treatment with drugs such as antidepressants, analgesics and anti-inflammatory drugs can provide, patients, physicians and researchers are looking for new main or adjuvant treatments, pharmacological and non-pharmacological (DE SOUSA BRAZ et al. al., 2011). In this context, it has been seen that the use of Cannabis sativa as a therapeutic option in fibromyalgia is promising, especially in reducing the pain caused by the disease and also the adjuvant symptoms, such as depression and sleep disorders (YASSIN; ORON; ROBINSON, 2019). This result must occur due to the action of cannabinoids, such as CBD and THC, on cannabinoid receptors distributed in peripheral nerves, spinal cord and supraspinal region, sites responsible for the reception, transmission and perception of pain (STE-MARIE et al., 2012). Currently, cannabinoids are considered safe analgesics with considerable efficacy, which demonstrates potential as a therapeutic option in the treatment of chronic pain, particularly in patients refractory to other treatments (HAUSER et al., 2018). In addition to its action on the painful mechanisms of fibromyalgia, the antidepressant effects of Cannabis are of great value in the treatment of fibromyalgia. These effects are explained by the modulation on serotonin 5-HT1A receptors, which has its effect exerted especially by CBD (ESPEJO-PORRAS et al., 2013).
Considering that research has reported the effects of phytocannabinoids on the painful symptoms of fibromyalgia (HAUSER et al., 2018), the hypotheses of the present study are:
Primary hypothesis: The dose-response curve and ED50 for the primary outcome, which is related to pain intensity, will be determined in the dose range between 0.1 and 10mg/day. The sensation of pain will be significantly reduced in participants receiving oral solution containing CBD/THC 10mg/day compared to those who will receive placebo.
Secondary hypothesis: There will be a reduction in pain catastrophizing, as well as an improvement in the acceptance and action rate related to pain, a reduction in depression, an improvement in sleep latency and quality, a reduction in insomnia and an increase in the quality of life in patients treated with oral solution containing CBD/THC 10mg/day compared to those receiving placebo.
Supporting Hypothesis: The tested CBD/THC solution will show efficacy and safety with no serious adverse effects.
详细描述
Patients with fibromyalgia will be recruited from tertiary health care establishments, specifically patients treated in the area of rheumatology, for eligibility assessment according to inclusion and exclusion criteria by the rheumatologist participating in this study, Osvaldo Haider Jr (CRM- PR 22274). It is important to point out that the patients' participation in the study will be voluntary, with no expectation of remuneration of any kind.
Recruitment for the two stages will follow these steps:
The first recruitment, in tertiary health care centers, in the rheumatology specialty, will start after approval of this project by the ethics committee; Dissemination of the study will be carried out via social networks and direct dissemination to doctors and tertiary health care clinics, which serve the rheumatology specialty; Enrolled volunteers must attend the evaluation for the inclusion and exclusion criteria, which will be carried out at the 3F Clinical Trials research center in a reserved environment at the clinical research centers contracted by 3F Clinical Trials; Patients must come with a medical report attesting to the diagnosis of fibromyalgia; The clinical evaluation, to meet the inclusion and exclusion criteria, will be performed under the supervision of the Rheumatologist Principal Investigator (PI) of this study, Osvaldo Haider Jr (CRM-PR 22274). Assessments of clinical symptoms, history will be performed, and the patient will be referred for laboratory tests of renal and hepatic profile. Additionally, women of childbearing age will undergo a biochemical hCG test. Additional tests for diagnostic confirmation or confirmation of any inclusion and exclusion criteria from the study may be requested; If there is a need for analysis of exams or the patient's medical history, it will be formally requested to the tertiary care center, where the patient undergoes his regular treatment, according to the requirements of the place, and according to the data use term. on file, the data will be kept confidential; Patients who are able to participate in the study, according to a clinical rheumatological evaluation, will undergo a pharmaceutical evaluation, carried out by the pharmacist responsible for this study, Ma. Ana Carolina Martins (e-CRF-PR 29255), to analyze the criteria in relation to the previous use of Cannabis, drug interactions in conventional treatment, possible reports that may exclude the patient from the study; Being able to participate in the study, the selected patients must read the informed consent; Patients will be informed that the project is placebo-controlled, and that this allocation to active treatment or placebo is random and double-blind; Agreeing with the terms, the patient will sign the informed consent in two copies, one for him and another for the researcher.
Participants will undergo a variety of examinations, questionnaires and tests during screening, enrollment and allocation, in-intervention assessments, final treatment assessment and for a post-trial period monitoring period. It is noteworthy that the evaluations performed through the clinical questionnaires established in this protocol will be made by telephone.
The following tests and protocols will be used: Pregnancy Test and Vital Signs; Pain; Depression; Sleep; Quality of life; Adverse Effects Monitoring; Laboratory; Tests.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The placebo will match the study drug in odor, taste, color and appearance to ensure proper masking. Eligible patients included in the pre-randomization period will be double-blind randomized in a 1:1:1:1 ratio between the experimental groups, by a biostatistician who is not involved in data collection nor analysis, to receive the CBD/THC solution at doses of 0.1mg/day, 1mg/day, 10mg/day, or placebo. A randomization sequence will be generated by computer, which creates identification codes necessary for the correct labeling of the drug and allocation of the patients in the experimental groups (https://www.sealedenvelope.com). This code will be adopted in the Case Report Form of the patient. The designation of the experimental group will be known by the data analysts, but hidden from the participants and the team involved with the treatment and research.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Previous diagnosis of fibromyalgia based on the pharmacological criteria of the American College of Rheumatology, 2016 to fibromyalgia, having received three months of pharmacological treatment without relevant clinical improvement;
- •Adult individuals (aged 18 to 75 years) with a mean pain intensity greater than or equal to 7 on the FIQ numerical pain scale (Fibromyalgia Impact Questionnaire);
- •No use of Cannabis or its derivatives (THC and CBD) in any systemic administration route in the last six months;
- •Capability to read, write and speak in Portuguese (Brazil);
- •Sign the ICF (Informed Consent Form).
排除标准
- •Pregnancy or breastfeeding;
- •Any known pathology, in an advanced stage, associated with the locomotor system (arthritis, osteoarthritis, uric acid);
- •Neurological disorders;
- •Previously reported renal disorders or changes in the exams during the pre-randomization stage;
- •Previously reported liver disorders or changes in tests during the pre-randomization stage;
- •Peripheral neuropathy;
- •Known serious cardiovascular disease (uncontrolled hypertension, heart failure, cardiac pacemaker);
- •Medical decision that participation in the study is not in the best interest of the patient;
- •Making previous use of cannabinoids by any route of administration;
- •Diagnosis of alcohol dependence;
- •Usage of psychotomimetic drugs or narcotics;
- •Having participated in research projects in the two months prior to the beginning of the study;
- •Having a history or having first-degree relatives with a history of psychosis in any level at least once in their lifetime;
- •Inappropriate metabolic profile of THC or CBD cannabinoids for the use of the test doses in this study, observed by pharmacogenetic testing.
研究组 & 干预措施
Placebo
10 participants will receive placebo (vehicle). The placebo will match the study drug in odor, taste, color and appearance. The administration will occur daily, once a day, during the night period, before going to bed and 30 minutes after the meal, during the next 120 days.
干预措施: Placebo (Drug)
cannabidiol and tetrahydrocannabinol 1:1 (0.1 mg/ml)
10 participants will receive CBD and THC in the same concentration (1:1) (0.1 mg/ml). The administration will occur daily, once a day, during the night period, before going to bed and 30 minutes after the meal, during the next 120 days.
干预措施: cannabidiol and tetrahydrocannabinol (Drug)
cannabidiol and tetrahydrocannabinol 1:1 (1.0 mg/ml)
10 participants will receive CBD and THC in the same concentration (1:1) (1.0 mg/ml). The administration will occur daily, once a day, during the night period, before going to bed and 30 minutes after the meal, during the next 120 days.
干预措施: cannabidiol and tetrahydrocannabinol (Drug)
cannabidiol and tetrahydrocannabinol 1:1 (10.0 mg/ml)
10 participants will receive CBD and THC in the same concentration (1:1) (10.0 mg/ml). The administration will occur daily, once a day, during the night period, before going to bed and 30 minutes after the meal, during the next 120 days.
干预措施: cannabidiol and tetrahydrocannabinol (Drug)
结局指标
主要结局
Dose-response curve and median effective dose
时间窗: Within 120 days
The primary outcome is the dose-response curve and median effective dose (ED50) in relation to the change in pain intensity within the dose range determined in this study, compared to placebo, as measured by the McGill Questionnaire.
次要结局
- Sleep quality(Within 120 days)
- Depressive symptoms(Within 120 days)
- Pain catastrophizing(Within 120 days)
- Insomnia Severity(Within 120 days)
- Acceptance in relation to pain(Within 120 days)
- Daytime sleepiness(Within 120 days)
- Sleep duration(Within 120 days)