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.
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (推定)
80
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：José Wilson N V Andrade, MD
- 電話番号：+55 11 971905328
- メール：dr.jwilsonandrade@gmail.com
研究連絡先のバックアップ
- 名前：Alethéia B P Barbosa, PhD
- 電話番号：+55 11 97247-1484
- メール：abpablos@gmail.com
研究場所
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São Paulo
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São Paulo、São Paulo、ブラジル、09130-040
- Projeto Shalom
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コンタクト：
- Alethéia B P Barbosa, PhD
- 電話番号：+55 11 97247-1484
- メール：abpablos@gmail.com
-
コンタクト：
- José Wilson N V Andrade, MD
- 電話番号：+ 55 11 971905328
- メール：dr.jwilsonandrade@gmail.com
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-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
いいえ
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：クロスオーバー割り当て
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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.
|
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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プラセボコンパレーター：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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change From Period Baseline in Chronic Pain Intensity on the Visual Analog Scale
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change From Period Baseline in Sleep Quality on the Pittsburgh Sleep Quality Index.
時間枠：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.
時間枠：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.
時間枠：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.
時間枠：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.
時間枠：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.
時間枠：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.
時間枠：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.
時間枠：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.
時間枠：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.
時間枠：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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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
協力者
捜査官
- 主任研究者：Alethéia B P Barbosa, PhD、Universidade Presbiteriana Mackenzie
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
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研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (推定)
2026年9月1日
一次修了 (推定)
2027年9月1日
研究の完了 (推定)
2027年12月1日
試験登録日
最初に提出
2026年8月20日
QC基準を満たした最初の提出物
2026年8月20日
最初の投稿 (実際)
2026年8月24日
学習記録の更新
投稿された最後の更新 (実際)
2026年8月26日
QC基準を満たした最後の更新が送信されました
2026年8月24日
最終確認日
2026年8月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- UPM-BONE-RELIEF-01
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
いいえ
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
いいえ
米国FDA規制機器製品の研究
いいえ
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