Full-Spectrum Cannabis Extract for Chronic Pain and Bone Health Biomarkers in Women (ORION)
Evaluation of Bone Turnover Biomarkers, CB2 and TRPV1 Polymorphisms as Potential Preventive Data in Osteoporosis and Perception of Improvement in Quality of Life in Women With Chronic Pain Treated With Medicinal Cannabis
Chronic pain disproportionately affects women and may coexist with impaired bone health, particularly during midlife and after menopause.
The endocannabinoid system is involved in pain modulation and bone homeostasis; however, clinical studies that integrate pain outcomes, bone-related biomarkers, genetic variants, and salivary endocannabinoids remain limited.This randomized, triple-masked, placebo-controlled crossover trial will evaluate the effects of a full-spectrum medicinal cannabis extract with a cannabidiol to tetrahydrocannabinol ratio of 5:1 on chronic pain in women aged 45 to 80 years with chronic pain refractory to conventional treatment.
Eighty participants will be randomly assigned to one of two treatment sequences: full-spectrum cannabis extract followed by matching placebo, or matching placebo followed by full-spectrum cannabis extract.
The treatment periods, washout interval, and visit schedule will follow the final approved protocol.The primary outcome is change in chronic pain intensity measured using the Visual Analog Scale.
Secondary outcomes include quality of life, sleep quality, functional impact, bone health biomarkers, bone mineral density measured by dualenergy X-ray absorptiometry, salivary endocannabinoids, the association of CB and TRPV genetic variants with treatment response, and adverse events.
The study aims to generate evidence on the clinical effects and biological correlates of medicinal cannabis therapy in women with chronic pain.
研究概览
详细说明
This is a randomized, triple-masked, placebo-controlled crossover clinical trial conducted in women aged 45 to 80 years with moderate to severe chronic pain that has persisted for at least 3 months and has not responded adequately to conventional pharmacological or non-pharmacological treatments.
Participants will be randomlyallocated in permuted blocks to one of two treatments sequences.
Sequence A will receive a full-spectrum medicinal cannabis extract with a cannabidiol to tetrahydrocannabinol ratio of 5:1 during the first treatment period, followed by a protocol-defined washout interval and matching placebo during the second treatment period.
Sequence B will receive matching placebo during the first treatment period, followed by the washout interval and the full-spectrum medicinal cannabis extract during the second treatment period.
The study product will be administered orally as softgel capsules.
The target daily dose is 25 milligrams of cannabidiol and 5 milligrams of tetrahydrocannabinol. Dose titration during the first 2 weeks of each active treatment period will follow the final approved protocol.Participants, care providers, investigators, and outcome assessors will remain masked to treatment assignment as operationally applicable.
Randomization will use a computer-generated sequence with permuted blocks of 4 and allocation concealment through opaque, sealed envelopes.
The product and matching placebo will be supplied in indistinguishable presentations.Clinical evaluations will include pain intensity, quality of life, functional impact, sleep quality, concomitant medications, adherence, and adverse events.
Laboratory assessments will include safety tests, selected bone metabolism biomarkers, inflammatory markers, and oxidative stress biomarkers.
Bone mineral density and body composition will be assessed using dualenergy X-ray absorptiometry at protocol-defined baseline and final visits.
Genetic analysis will evaluate CB and TRPV variants.
Salivary anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleoylethanolamide will be quantified using liquid chromatography coupled with tandem mass spectrometry according to the final sample collection schedule.The primary efficacy analysis will compare pain outcomes across cannabis and placebo treatment periods while accounting for the crossover design.
Secondary analyses will evaluate changes in patient-reported outcomes and biomarkers, treatment safety, and associations between genetic variants or salivary endocannabinoid profiles and treatment response.
研究类型
介入性
注册 (估计的)
80
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习联系方式
- 姓名：José Wilson N V Andrade, MD
- 电话号码：+55 11 971905328
- 邮箱：dr.jwilsonandrade@gmail.com
研究联系人备份
- 姓名：Alethéia B P Barbosa, PhD
- 电话号码：+55 11 97247-1484
- 邮箱：abpablos@gmail.com
学习地点
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São Paulo
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São Paulo、São Paulo、巴西、09130-040
- Projeto Shalom
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接触：
- Alethéia B P Barbosa, PhD
- 电话号码：+55 11 97247-1484
- 邮箱：abpablos@gmail.com
-
接触：
- José Wilson N V Andrade, MD
- 电话号码：+ 55 11 971905328
- 邮箱：dr.jwilsonandrade@gmail.com
-
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
不
描述
Inclusion Criteria:
- Female sex, age 45 to 80 years
- Moderate to severe chronic pain, defined as a pain score of at least 4 on a 0 to 10 Visual Analog Scale, persisting for more than 3 months
- Documented inadequate response to at least 2 classes of analgesic treatments or non-pharmacological treatments
- Willingness to abstain from smoked cannabis and non-study cannabinoid products during the study
- Ability to understand the informed consent form and study questionnaires
- Willingness and ability to attend scheduled visits and biological sample collections during the study follow-up period
Exclusion Criteria:
- Cognitive impairment that precludes understanding of the informed consent form or study questionnaires
- Uncontrolled psychiatric condition, including uncontrolled psychotic disorder or bipolar disorder
- Pregnancy, breastfeeding, or intention to become pregnant during the study
- Current use of medicinal cannabis, smoked cannabis, or other cannabinoid products
- Known hypersensitivity to cannabinoids or formulation excipients
- Clinically significant hepatic impairment, defined as aspartate aminotransferase or alanine aminotransferase greater than 3 times the upper limit of normal, or severe heart failure classified as New York Heart Association class III or IV
- History of substance use disorder that, in the investigator's judgment, may interfere with study participation
- Use of medications that may interfere with bone metabolism, including bisphosphonates, systemic corticosteroids, or sex hormones, within 6 months before enrollment
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：交叉作业
- 屏蔽：三倍
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Cannabis Extract Then Placebo
Participants receive oral full-spectrum cannabis extract with a cannabidiol to tetrahydrocannabinol ratio of 5:1 during Treatment Period 1, followed by the protocol-defined washout interval and matching placebo during Treatment Period 2.
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Oral softgel capsule containing full-spectrum medicinal cannabis extract with a cannabidiol to tetrahydrocannabinol ratio of 5:1.
The target daily dose is 25 milligrams of cannabidiol and 5 milligrams of tetrahydrocannabinol. Participants will receive the study product once daily in the evening, with gradual dose titration during the first 2 weeks of each active treatment period, according to the final approved protocol.
The product will be administered for the duration of each protocol-defined active treatment period.
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安慰剂比较：Placebo Then Cannabis Extract
Participants receive matching placebo during Treatment Period 1, followed by the protocol-defined washout interval and oral full-spectrum cannabis extract with a cannabidiol to tetrahydrocannabinol ratio of 5:1 during Treatment Period 2.
|
Oral softgel capsule containing full-spectrum medicinal cannabis extract with a cannabidiol to tetrahydrocannabinol ratio of 5:1.
The target daily dose is 25 milligrams of cannabidiol and 5 milligrams of tetrahydrocannabinol. Participants will receive the study product once daily in the evening, with gradual dose titration during the first 2 weeks of each active treatment period, according to the final approved protocol.
The product will be administered for the duration of each protocol-defined active treatment period.
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Change From Period Baseline in Chronic Pain Intensity on the Visual Analog Scale
大体时间：At the baseline and end of each treatment period, approximately 6 months per period.
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Chronic pain intensity will be measured using a 0 to 10 Visual Analog Scale, where 0 indicates no pain and 10 indicates the worst imaginable pain.
The baseline score will be the mean pain intensity reported over the preceding 7 days.
A clinical response is defined as a reduction of at least 30 percent from the baseline score of the corresponding treatment period.
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At the baseline and end of each treatment period, approximately 6 months per period.
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Change From Period Baseline in Sleep Quality on the Pittsburgh Sleep Quality Index.
大体时间：At baseline and at 3 and 6 Months each treatment period.
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Sleep quality will be measured using the Pittsburgh Sleep Quality Index (PSQI), a self-reported instrument with a global score from 0 to 21.
Higher scores indicate worse sleep quality.
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At baseline and at 3 and 6 Months each treatment period.
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Change From Period Baseline in Health-Related Quality of Life on the 36-Item Short Form Survey.
大体时间：At baseline and at Months 3 and 6 of each treatment period.
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Health-related quality of life will be assessed using the Medical Outcomes Study 36-Item Short Form Survey (SF-36).
Scores are calculated for 8 domains from 0 to 100; higher scores indicate better health-related quality of life.
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At baseline and at Months 3 and 6 of each treatment period.
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Change From Period Baseline in Pain-Related Quality of Life on the WHOQOL-Pain Instrument.
大体时间：At baseline and at Months 3 and 6 of each treatment period.
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Pain-related quality of life will be assessed using the Portuguese version of the WHOQOL-Pain instrument.
Scoring and interpretation will follow the validated instrument manual.
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At baseline and at Months 3 and 6 of each treatment period.
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Change From Period Baseline in Fibromyalgia Impact Questionnaire Score Among Participants With Fibromyalgia.
大体时间：At baseline and at Months 3 and 6 of each treatment period.
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Functional impact among participants with a clinical diagnosis of fibromyalgia will be assessed using the Fibromyalgia Impact Questionnaire (FIQ).
The scale will be scored according to the validated Portuguese version; higher scores indicate greater disease impact.
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At baseline and at Months 3 and 6 of each treatment period.
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Change From Baseline in Bone Mineral Density Measured by Dual-Energy X-Ray Absorptiometry.
大体时间：At baseline and at the final study visit, approximately 12 months after enrollment.
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Bone mineral density and body composition will be assessed using dual-energy X-ray absorptiometry (DXA).
Bone mineral density will be reported in grams per square centimeter and interpreted using T-scores according to applicable clinical criteria.
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At baseline and at the final study visit, approximately 12 months after enrollment.
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Change From Period Baseline in Serum Bone Turnover Biomarkers.
大体时间：At baseline and at protocol-defined follow-up visits through final study completion, approximately 12 months.
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Serum bone health biomarkers will include the final protocol-specified panel of alkaline phosphatase, total and ionized calcium, 25-hydroxyvitamin D, and parathyroid hormone.
If procollagen type 1 N-terminal propeptide and C-terminal telopeptide are retained in the final protocol, they should be listed here explicitly.
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At baseline and at protocol-defined follow-up visits through final study completion, approximately 12 months.
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Association of CB2 and TRPV1 Genetic Variants With Pain Treatment Response.
大体时间：Genotyping at baseline; association with pain response through the end of each treatment period, approximately 12 months.
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Genotyping of cannabinoid receptor 2 (CB2/CNR2) and transient receptor potential vanilloid 1 (TRPV1) variants will be performed using real-time polymerase chain reaction.
Associations between genotype or haplotype and the prespecified Visual Analog Scale pain response will be evaluated.
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Genotyping at baseline; association with pain response through the end of each treatment period, approximately 12 months.
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Change From Baseline in Salivary Endocannabinoid Concentrations.
大体时间：Use the final collection schedule; do not submit this entry until the protocol is harmonized as baseline-only or serial sampling.
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Salivary concentrations of anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleoylethanolamide will be quantified by liquid chromatography-tandem mass spectrometry and reported in nanograms per milliliter.
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Use the final collection schedule; do not submit this entry until the protocol is harmonized as baseline-only or serial sampling.
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Number of Participants With Treatment-Emergent Adverse Events.
大体时间：From first study product administration through the end of each treatment period, approximately 6 months per period.
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Adverse events will be collected through clinical visits and weekly remote pharmacotherapeutic monitoring.
Events will be classified by severity, seriousness, relatedness to study treatment, and treatment period.
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From first study product administration through the end of each treatment period, approximately 6 months per period.
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Change From Period Baseline in Hepatic and Renal Safety Laboratory Values.
大体时间：At baseline and at protocol-defined follow-up visits through final study completion, approximately 12 months.
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Safety laboratory assessments will include protocol-specified hepatic and renal tests, including aspartate aminotransferase, alanine aminotransferase, urea, and creatinine.
Results will be reported in standard laboratory units.
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At baseline and at protocol-defined follow-up visits through final study completion, approximately 12 months.
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
合作者
调查人员
- 首席研究员：Alethéia B P Barbosa, PhD、Universidade Presbiteriana Mackenzie
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研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (估计的)
2026年9月1日
初级完成 (估计的)
2027年9月1日
研究完成 (估计的)
2027年12月1日
研究注册日期
首次提交
2026年8月20日
首先提交符合 QC 标准的
2026年8月20日
首次发布 (实际的)
2026年8月24日
研究记录更新
最后更新发布 (实际的)
2026年8月26日
上次提交的符合 QC 标准的更新
2026年8月24日
最后验证
2026年8月1日
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- UPM-BONE-RELIEF-01
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
不
药物和器械信息、研究文件
研究美国 FDA 监管的药品
不
研究美国 FDA 监管的设备产品
不
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