A Randomized Controlled Trial of Oral CBD for the Treatment of Upper Extremity Musculoskeletal Pain

Обзор

The goal of this clinical trial is to learn about the use of cannabidiol (CBD) capsules as a treatment for musculoskeletal pain. CBD is commonly being used as an over-the-counter treatment for musculoskeletal pain. Clinical trials have demonstrated a pain-relief benefit for hand and wrist osteoarthritis with topical CBD, however patients prefer oral CBD and no clinical trial has been performed to establish efficacy of oral CBD in humans for upper extremity musculoskeletal pain. The main questions it aims to answer are: Is CBD more effective than placebo at relieving pain for upper extremity musculoskeletal pain ? Is CBD safe for participants with upper extremity musculoskeletal pain? Participants will: take 4 weeks of daily CBD capsules take 4 weeks of daily placebo capsules answer surveys about how they are feeling and functioning. Participants will \[describe the main tasks participants will be asked to do, interventions they'll be given and use bullets if it is more than 2 items\].

Подробное описание

This randomized controlled trial of CBD will investigate the therapeutic potential of CBD as an oral treatment for the treatment of pain of upper extremity musculoskeletal pain. Rationale: CBD is commonly being used as an over-the-counter treatment for musculoskeletal pain. Clinical trials have demonstrated a pain-relief benefit for hand and wrist osteoarthritis with topical CBD, however patients prefer oral CBD and no clinical trial has been performed to establish efficacy of oral CBD in humans for upper extremity musculoskeletal pain. Hypothesis: CBD is more effective than placebo for relieving pain and improving patient-reported outcomes for upper extremity musculoskeletal pain.

Study Design: The study design will be a double-blind, randomized controlled trial with crossover. Treatment will be blinded to the subjects and investigators. Patients will be randomly assigned 4 weeks of the CBD or control and then crossover to the other condition for 4 additional weeks. Patients will take one oral capsule twice daily, once in the morning and once in the evening. Subjects will be advised to observe for physiologic changes, skin changes, or other adverse effects.

Вмешательства

• Препарат Cannabidiol (CBD)
  25 mg capsule twice daily
• Препарат Placebo
  25 mg capsule twice daily

Первичные конечные точки

• Change from Baseline in Pain on the Visual Analog Pain (VAS) Score [Срок оценки: Baseline and Week 4, Week 6]
• Change from Baseline in Pain on the Visual Analog Pain (VAS) Score - Crossover Condition [Срок оценки: Baseline and Week 4, Week 6]
• Change from Baseline in Normal Function on the Single Assessment Numerical Evaluation (SANE) Score [Срок оценки: Baseline and Week 4, Week 6]
• Change from Baseline in Normal Function on the Single Assessment Numerical Evaluation (SANE) Score - Crossover Condition [Срок оценки: Baseline and Week 4, Week 6]
• Change from Baseline in Quality of Life on the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health-10 Score [Срок оценки: Baseline and Week 4, Week 6]
• Change from Baseline in Quality of Life on the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health-10 Score - Crossover Condition [Срок оценки: Baseline and Week 4, Week 6]
• Change from Baseline in Pain interference on the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference Score [Срок оценки: Baseline and Week 4, Week 6]
• Change from Baseline in Pain interference on the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference Score - Crossover Condition [Срок оценки: Baseline and Week 4, Week 6]
• Change from Baseline in Pain interference on the Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity (UE) Score [Срок оценки: Baseline and Week 4, Week 6]
• Change from Baseline in Pain interference on the Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity (UE) Score - Crossover Condition [Срок оценки: Baseline and Week 4, Week 6]

Вторичные конечные точки (12)

• Number of Participants With Treatment-Related Adverse Events [Срок оценки: Through study completion, an average of 12 weeks]
• Change from Baseline in the Mean Seated Trough Cuff Systolic Blood Pressure [Срок оценки: Baseline and Week 4]
• Change from Baseline in Heart Rate [Срок оценки: Baseline and Week 4]
• Change from Baseline in the Mean Seated Trough Cuff Systolic Blood Pressure [Срок оценки: Week 4 and Week 6]
• Change from Baseline in Heart Rate [Срок оценки: Week 4 and Week 6]
• Change from baseline in serum comprehensive metabolic panel (CMP) parameters: glucose, blood urea nitrogen (BUN), Creatinine, Calcium [Срок оценки: Through study completion, an average of 12 weeks]
• Change from baseline in serum liver panel parameters: Alanine transaminase (ALT), Alkaline phosphatase (ALP) and Aspartate aminotransferase (AST) [Срок оценки: Through study completion, an average of 12 weeks]
• Change from baseline in serum comprehensive metabolic panel (CMP) parameters: Chloride [Срок оценки: Through study completion, an average of 12 weeks]
• Change from baseline in serum comprehensive metabolic panel (CMP) parameters: Sodium, Potassium, Chloride, Carbon Dioxide [Срок оценки: Through study completion, an average of 12 weeks]
• Change from baseline in serum comprehensive metabolic panel (CMP) parameters: Bilirubin [Срок оценки: Through study completion, an average of 12 weeks]
• Change from baseline in serum comprehensive metabolic panel (CMP) parameters: Prothrombin time- International normalized ratio (PT-INR) [Срок оценки: Through study completion, an average of 12 weeks]
• Change from baseline in serum comprehensive metabolic panel (CMP) parameters: Protein, Albumin [Срок оценки: Through study completion, an average of 12 weeks]

Критерии участия

Критерии включения

• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, aged 18 years or older.
• Daily visual analog pain score >5/10 and <9/10.
• Duration of pain for greater than or equal to 3 months.
• Presence of physician-diagnosed musculoskeletal pain in the upper extremities, including bone or joint-related pain, tendon or ligament-related pain, muscle-related pain, or fibromyalgia or physician-diagnosed postoperative pain in a discrete body region, limited to upper extremities.
• For females, must be willing to use an approved form of birth control during this study. Acceptable forms of birth control:

• Norplant
• Sterilization
• IUD (intrauterine device)
• Birth Control Patch
• Depo-Provera

The following may be used if combined with other birth control methods:

• Condoms
• Diaphragm
• Jellies or foam
• Sponge
• Cervical cap
• For males, must be willing to not father a baby for the duration of the study and for 90 days after the last dose of study drug, or donate to a sperm bank during this time. Must be willing to use an approved form of birth control during this time. Acceptable forms of birth control:

• Condoms
• Sterilization

Критерии исключения

• Subject does not speak or read English fluently.
• Subject is blind.
• Severe cardiac, pulmonary, liver and /or renal disease, or any other major organ dysfunction.
• Subject with a history of symptoms (e.g., dizziness, light-headedness, blurred vision, palpitations, weakness, syncope) related to a drop in blood pressure due to postural changes.
• Coumadin use at time of screening.
• History of mental illness.
• Subjects who are incarcerated.
• Subjects who satisfy any DSM-V criteria for current psychiatric illness such as bipolar disorder, depression, anxiety, schizophrenia, psychosis, substance use disorder or any other psychiatric diagnosis
• Subjects who have used intra-articular corticosteroids 30 days prior to screening.
• History of drug or substance abuse.
• Pre-existing CBD product usage currently (or within the prior 3 months) using recreational or medicinal cannabis, any cannabinoid-based medications, and is unwilling to abstain for the duration of the study.
• Subject has had a corticosteroid injection ≤ 60 days prior.
• Subjects who are unwilling to agree to no opioid medications or topical analgesic medications during the study period.
• Any woman of child bearing potential or male patient's partner unwilling to ensure that they or their partner use effective contraception, for example, hormonal contraception, double barrier, intra-uterine device, during the study and for females, through 30 days thereafter, and for males, three months thereafter.
• Any male not willing to avoid donating sperm during the duration of the study treatment period and for three months thereafter.
• Any patient with aberrant liver function as defined by either of the following:

• ALT >5x ULN or total bilirubin>2×ULN
• ALT or AST>3 × ULN and total bilirubin>2xULN or INR >1.5
• Participants within 14 days of the study procedure taking prescription or non-prescription medication which are substrates of CYP3A4 :

• Itraconazole,
• Ketoconazole,
• Azamulin,
• Troleandomycin,
• Verapamil,
• John's wart,
• Phenobarbital,
• Participants within 14 days of the study procedure taking prescription or non-prescription medication which are substrates of CYP2C19:

• Nootkatone,
• Ticlopidine,
• Rifampin,
• Omeprazole),
• Subjects taking prescription or non-prescription medication which are substrates of CYP2C8:

• Montelukast,
• Quercetin,
• Phenelzine,
• Rifampin,
• Clopidogrel) ,
• Participants within 14 days of the study procedure taking prescription or non-prescription medication which are substrates ofCYP2C9:

• Sulfaphenazole,
• Tienilic acid,
• Carbamazepine,
• Apalutamide,
• Fluconazole,
• Celecoxib
• Participants within 14 days of the study procedure taking prescription or non-prescription medication which are substrates of CYP1A2:

• alpha-Naphthoflavone,
• Furafylline,
• Phenytoin,
• Rifampin,
• Ritonavir,
• smoking,
• Teriflunomide,
• Ciproflaoxacin,
• oral contraceptives,
• Allopurinol
• Participants within 14 days of the study procedure taking prescription or non-prescription medication which are substrates of CYP2B6:

• Sertraline,
• Phencyclidine,
• Thiotepa,
• Ticlopidine,
• Carbamazepine,
• Efavirenez,
• Rifampin,
• Bupropion.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Virginia — Charlottesville

Публикации

• Russo E.B., Mathre M.L., Byrne A., Velin R., Bach P.J., Sanchez-Ramos J., et. al.: Chronic cannabis use in the compassionate investigational new drug program: an examination of benefits and adverse effects of legal clinical cannabis. J Cannabis Ther 2002; 2: pp. 3-57.
• Stockings E, Zagic D, Campbell G, Weier M, Hall WD, Nielsen S, Herkes GK, Farrell M, Degenhardt L. Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence. J Neurol Neurosurg Psychiatry. 2018 Jul;89(7):741-753. doi: 10.1136/jnnp-2017-317168. Epub 2018 Mar 6. PMID 29511052
• Bruni N, Della Pepa C, Oliaro-Bosso S, Pessione E, Gastaldi D, Dosio F. Cannabinoid Delivery Systems for Pain and Inflammation Treatment. Molecules. 2018 Sep 27;23(10):2478. doi: 10.3390/molecules23102478. PMID 30262735
• Fader L, Scharf Z, DeGeorge BR Jr. Assessment of Medical Cannabis in Patients With Osteoarthritis of the Thumb Basal Joint. J Hand Surg Am. 2023 Mar;48(3):257-262.e1. doi: 10.1016/j.jhsa.2021.10.018. Epub 2021 Dec 8. PMID 34893392
• Ware MA, Wang T, Shapiro S, Collet JP; COMPASS study team. Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). J Pain. 2015 Dec;16(12):1233-1242. doi: 10.1016/j.jpain.2015.07.014. Epub 2015 Sep 16. PMID 26385201
• Heineman JT, Forster GL, Stephens KL, Cottler PS, Timko MP, DeGeorge BR Jr. A Randomized Controlled Trial of Topical Cannabidiol for the Treatment of Thumb Basal Joint Arthritis. J Hand Surg Am. 2022 Jul;47(7):611-620. doi: 10.1016/j.jhsa.2022.03.002. Epub 2022 May 28. PMID 35637038
• MacCallum CA, Russo EB. Practical considerations in medical cannabis administration and dosing. Eur J Intern Med. 2018 Mar;49:12-19. doi: 10.1016/j.ejim.2018.01.004. Epub 2018 Jan 4. PMID 29307505
• Arzimanoglou A, Brandl U, Cross JH, Gil-Nagel A, Lagae L, Landmark CJ, Specchio N, Nabbout R, Thiele EA, Gubbay O, The Cannabinoids International Experts Panel; Collaborators. Epilepsy and cannabidiol: a guide to treatment. Epileptic Disord. 2020 Feb 1;22(1):1-14. doi: 10.1684/epd.2020.1141. PMID 32096470

Идентификаторы

NCT: NCT06695195 · 301881

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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