Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05283161 |
| Other study ID # |
04200240 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 2/Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
April 15, 2022 |
| Est. completion date |
November 20, 2022 |
Study information
| Verified date |
April 2022 |
| Source |
FG Brasil LTDA |
| Contact |
Fernando C Dos Santos, PhD |
| Phone |
+55 (45) 3031-2262 |
| Email |
contato[@]3fclinicaltrials.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
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.
Description:
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.
The pre-randomization period will take place in weeks -8 to 0 in order to make sure that all
participants meet all the inclusion criteria. Participants who are under pharmacological
treatment must have their treatments stable for at least 60 days and not make changes to
these treatments during the clinical trial, without such procedure being duly registered.
Patients eligible for the study, following the inclusion and exclusion criteria, will be
randomized in a 1:1:1:1 ratio to receive CBD/THC 1:1 (0.1 mg/ml) (n=10), CBD/THC 1:1 (1.0
mg/ml) (n=10), CBD/THC 1:1 (10 mg/ml) (n=10) or placebo (vehicle) (n=10), daily, once a day
day. The treatment will have a total duration of 120 days.
The dose was chosen based on preliminary results of pilot studies conducted by this research
group (with unpublished results) and also according to the characteristics of the drug
produced by the sponsor. In addition, evidence has shown that doses in previously published
studies have doses within this range or even above the concentration determined for our study
(see item 11.1).
The clinical study will have a baseline assessment (T0), one day before the start of the
intervention with the solution. The tools will be reapplied after 15 (T1), 30 (T2), 60 (T3),
90 (T4) and 120 (T5) days of intervention. Medical monitoring of vital signs and clinical
evidence of potential adverse effects will take place throughout the study. In this trial,
for ethical reasons, patients will not be advised to discontinue the pharmacological
treatment currently in use (e.g., opioids, antidepressants, benzodiazepines, gabapentinoids,
anti-inflammatory drugs, or other non-opioid analgesics).
The CBD/THC solution will be administered to participants as an oral solution. The drug will
be provided by the company FG Brasil LTDA, under the trade name Aura Pharma, which is a
company that imports cannabinoid products and sponsors this study.
The product consists of a solution containing the phytopharmaceuticals CBD and THC, both at a
concentration of 10mg/mL. The dilution vehicle is MCT (medium chain triglycerides) oil.
Product development is carried out at Schibano Pharma AG Tüfi, 450 - Wald Schönengrund -
9105, Switzerland, and is obtained under Good Manufacturing Practices (GMP) protocols,
ensuring a level of pharmaceutical quality for human use, and free from the addition of
isolated substances of synthetic or semi-synthetic origin.
The sponsor will also provide the placebo, which consists of the vehicle without the addition
of CBD and THC phytopharmaceuticals, maintaining the same organoleptic aspects of the CBD/THC
solution.
The solution will be provided by the study sponsor, packaged in 10 mL vials, along with a
dosing syringe (with graduation lines) for oral administration. The patient will be
instructed to store the bottle in a place with a temperature of up to 30°C, dry, protected
from light and heat, and out of the reach of children.
Dilution will be carried out in the same vehicle as the base drug, which will be provided by
the sponsor, for doses of 0.1 and 1mg/ml. Thus, all patients will aspirate the equivalent
volume to be administered (1mL/day) from their own bottle, corresponding to: (i) Group 1:
0.1mg of CBD and 0.1mg of THC; (ii) Group 2: 1mg of CBD and 1mg of THC; (iii) Group 3: 10mg
of CBD and 10mg of THC; (iv) Group 4: placebo/vehicle. The time of administration will be
daily, in the evening before going to bed, and 30 minutes after the meal. Participants will
be instructed to wash the syringe with water and detergent after use, and rinse thoroughly
with running water through repetitive aspirations.
It should be noted that a double quality control will be carried out, with physical-chemical
analysis, prior to the availability of the product for the study. The first quality review is
carried out by the product developer in Switzerland. Finally, the second quality analysis is
performed by Aura Pharma in Brazil.
Labeling and storage:
All study products will be labeled in English and Portuguese in accordance with local
regulations for investigational drugs.
A total of 40 patients will be required to detect a significant difference from treatment
with the standardized CBD/THC solution. We performed an a priori calculation using the effect
size described by Yanes et al. (2019) (Cohen's d = 0.58), considering an analysis of
covariance (ANCOVA) design for repeated measures, alpha (α) set at 5% and statistical power
(β) at 80%. In this case, we use the software GPower* 3.1.9.7 (Heinrich-Heine-Universityät,
Düsserldorf). The collection and preservation of clinical data complies with standard
requirements for data management and handling in accordance with the ICH/BPC. A secure
database will be established for the collection of clinical data through the e-CRF platform
via a secure connection at clinical research facilities and with traceable restricted access.
All data obtained during the study will be documented in the individual e-CRF. In case of
missing data, the reasons for this will be noted in the e-CRF.
Participant information collected in the e-CRF, but not recorded in the patient's files, will
be considered as source documents. Patient participation and any treatment-related AE in the
study will be documented in the e-CRF. No patient information, such as medical history and
medication history, will be collected before the informed consent has been obtained from the
patient. Information obtained directly from potential participants prior to obtaining the
informed consent (ie, during eligibility screening) will be recorded in the e-CFR, and this
information will be made available to researchers with the patients' permission.
The study will end when the last patient completes the last clinical evaluation at the end of
120 days of treatment, or the patient may for some reason discontinue the intervention and
choose to withdraw from the clinical trial. This protocol will be suspended or terminated if
the Principal Investigator, in agreement with the research team: Perceive that there is a
risk or harm to the health of voluntary participants, and this risk is directly associated
with the investigational drug and not provided in the informed consent; observe the
occurrence of a serious adverse event after signing the informed consent, which results in:
1) death; 2) threat or risk to life; 3) need for hospitalization; 4) prolongation of
preexisting hospitalization; 5) permanent disability or damage; or 6) a significant medical
occurrence that, based on appropriate medical judgment, may impair the participant's
exclusion criteria and/or require medical or surgical intervention to prevent any of the
other aforementioned occurrences. In case of termination or suspension of this study, all
participants will be informed, receive appropriate therapy and be followed up by the
responsible physician and research team.
