Chronic Migraine, HeadachePhase 2/3CAMTREANCT04989413
Cannabidiol 133mg + Cannabigerol 66mg + Tetrahydrocannabinol 4mg Vs Placebo As Adjuvant Treatment in Chronic Migraine -
A Phase 2/3 study testing Cannabidiol + Cannabigerol + Tetrahydrocannabinol 133/66/4mg in people with Chronic Migraine, Headache and Overuse Headache Medication, run by Hospital Israelita Albert Einstein at 1 site in Brazil.
Trial summary
To evaluate the effect of the cannabidiol (CBD) + cannabigerol (CBG) + tetrahydrocannabinol (THC) up to 133/66/4mg daily versus placebo as adjuvant treatment in chronic migraine (CM) patients under preventive treatment at a stable dose for at least 3 months who present at least 5 headaches day a month. Read more about this study
- Who is it for?
- Ages 25 to 65 years
- Conditions the study is for
- Chronic Migraine, Headache, Overuse Headache Medication
- What is being tested?
- Cannabidiol + Cannabigerol + Tetrahydrocannabinol 133/66/4mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 110 participants
- Where
- 1 siteBrazil
- Study dates
- 18 Oct 2022to 20 Feb 2025
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients of both sexes, 25 to 65 years old, with chronic migraine according to IHS Classification System, 3rd edition
- Undergoing preventive treatment in a stable dose of the preventive medication for at least 2 months, who have not used cannabidiol to treat migraine.
- At least 5 days of migraine/migraine like attacks in the baseline period (4 weeks)
- As preventive drugs propranolol, atenolol, topiramate, valproic acid/sodium valproate, levetiracetam, gabapentin, lamotrigine, pre-gabaline, flunarizine, amitriptyline, nortriptyline, clomipramine, candesartan, galcanezumab, erenumab, fremanezumab, botulinum toxin type A will be allowed. Patients whose preventive treatment for migraine is Botulinum Toxin Type A may participate in the study as long as the toxin application interval used is 4 months (duration of medication or placebo use) and who have already received treatment with toxin at least 2 times.
- If acute treatment is necessary, patients may use the medications as previously advised by the physician accompanying them, and may use common, combined painkillers, anti-inflammatory drugs, triptans, triptans combined with anti-inflammatory drugs, opioid analgesics.
Who cannot join
- Patients with active liver disease
- pregnancy and/or women who intend to become pregnant or who do not make adequate use of contraceptive therapy/methods
- breastfeeding women
- use of cannabis during the study, whether with therapeutic or recreational intentions
- patients who are without preventive treatment or who have undergone a dose change in preventive migraine treatment less than two months before V1 .
- Patients whose exclusive treatment for chronic migraine is Botulinum Toxin Type A at intervals of less than 4 months.
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- History of substance abuse or addiction, use of medical cannabis or products with CBD, CBG or THC in the last 30 days, history of allergy to CBD or related products
- elevated transaminases > 3x the normal value
- substance abusers
- patients using substances that are potent enzyme inducers, such as rifampicin, ketoconazole, theophylline, carbamazepine, phenytoin, phenobarbital and St. John's wort, clobazam, macrolides, verapamil, fluoxetine, amiodarone and tacrolimus.
- Patients using anticoagulant, like vitamin K anticoagulant medicines, as warfarin.
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Centro de Pesquisa Clinica Hospital Israelita Albert Einstein
São Paulo, São Paulo, 05653120
About this study
Official title: Randomized, Double Blind Clinical Trial to Study the Effect of Cannabidiol (CBD) 133mg + Cannabigerol (CBG) 66mg + Tetrahydrocannabinol (THC) 4mg a Day As Adjunctive Therapy in the Treatment of Chronic Migraine - CAMTREA TRIAL
To evaluate the effect of the cannabidiol (CBD) + cannabigerol (CBG) + tetrahydrocannabinol (THC) up to 133/66/4mg daily versus placebo as adjuvant treatment in chronic migraine (CM) patients under preventive treatment at a stable dose for at least 3 months who present at least 5 headaches day a month. CM patients of both sexes, between 25 and 65 years old, who have not had CBD and/or THC as a migraine treatment. Patients may be having migraine preventive treatment such as propranolol, atenolol, topiramate, valproic acid/sodium valproate, levetiracetam, gabapentin, lamotrigine, pre-gabaline, flunarizine, amitriptyline, nortriptyline, clomipramine, candesartan, galcanezumab, erenumab, fremanezumab, botulinum toxin type A. Acute treatment will follow patients doctor's prescription. Exclusion criteria: active liver disease or elevated liver transaminases> 3 times than the normal values, pregnancy, fertile age women without contraceptive treatment or who intend to get pregnant, patients without migraine preventive treatment or that changed the preventive treatment less than 3 months from the study start, substance abuse or addiction, use of medical cannabis or products with CBD or THC in the last 30 days or during study period, history of allergy or adverse reactions with the use of CBD or related products, substance users of liver enzymes inducers such as rifampicin, ketoconazole, theophylline, carbamazepine, phenytoin, phenobarbital and St. John's wort, clobazam, macrolides, verapamil, fluoxetine, amiodarone and tacrolimus. Patients on vitamin K anticoagulant medicines, as warfarin.
Randomization using a computacional system will stratify participants in each group by gender (F/M), age (25-34/35-44/45-54/55-65yo), headache days presented in the baseline month (5-10/11-15/16-20/21-25/26-30), overuse medication (yes or no). After randomization patients will be divided into two groups of 55 participants, who will receive CBD + CBG + THC up to a maximum daily dose of 133/66/4 mg or placebo for 12 weeks (V0 screening, V1 allocation, V4 final visit).
Read more
The main outcome is the reduction in frequency of headache days per 4 weeks between V1 and V4 compared to placebo. Secondary outcomes will be a reduction in duration and intensity of migraine attacks, amount of painkillers used and percentage of patients with a reduction greater than 50% on migraine days, 50% reduction in the other variables as MIDAS scores, HIT-6 scores, Beck's Anxiety and Depression Scales, Epworth Sleepiness Scales, and the scores at The Severity of Dependence Scale used as an indicator of overuse medication in this sample.
Clinical data will be registered on a personalized headache diary developed to this study using MyCap, from RedCap System, as an APP for daily entries using smartphones, androids or IOS system.
The clinical and laboratory data obtained in this study will comply with the objectives elaborated in the evaluation of the primary and secondary endpoints, the proposal of which is to publish the data regardless of the results obtained.
- Being tested
- Placebo oral drops, Cannabidiol + Cannabigerol + Tetrahydrocannabinol 133/66/4mg
- Medical subject headings
- Headache, Headache Disorders, Secondary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo oral dropsDrug
use of placebo for 12 weeks
Cannabidiol + Cannabigerol + Tetrahydrocannabinol 133/66/4mgDrug
use of cannabidiol + canabigerol + thc for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Cannabidiol + Cannabigerol + Tetrahydrocannabinol 133/66/4mg | Active comparator | Cannabidiol + Cannabigerol + Tetrahydrocannabinol in the maximum dosage of 133/66/4mg, divided in 2 doses of 66.5/33/2mg a day for 12 weeks. Each drop contain CBD/CBG/THC 1.66/0.8/0.05 mg, and medication will be titrated up as follow: day 1 to day 3 - 10 drops twice a day day 4 to day 6 - 20 drrops twice a day day 7 to day 9 - 30 drops twice a day from day 10 to the end of the study 40 drops twice a day Receives: Drug: Cannabidiol + Cannabigerol + Tetrahydrocannabinol 133/66/4mg |
| Placebo | Placebo comparator | Placebo capsules will be titrated up as follow:
day 1 to day 3 - 10 drops twice a day day 4 to day 6 - 20 drops twice a day day 7 to day 9 - 30 drops twice a day from day 10 to the end of the study 40 drops twice a day Receives: Drug: Placebo oral drops |
What is being measured
The primary outcome is the main question the study is designed to answer.
Migraine days
The primary outcome will be the reduction in migraine days observed between the baseline period (4 weeks before randomization) and the final visit 12 weeks of intervention (CBD+CBG+THC or placebo)
Measured: 16 weeks
Secondary outcomes (12)
Headache days
The primary outcome will be the reduction in headache days observed between the baseline period (4 weeks before randomization) and the final visit 12 weeks of intervention (CBD+CBG+THC or placebo)
Measured: 12 weeks
migraine duration
the attack duration in hours observed before and after the intervention (CBD+CBG+THC or placebo)
Measured: 12 weeks
migraine intensity
the migraine attack intensity measured in a 3 point scale (1- mild; 2 - moderate; 3 - severe) before and after the intervention (CBD+CBG+THC or placebo)
Measured: 12 weeks
pain medicine intake
the amount of pain medicine intake as needed before and after the intervention (CBD+CBG+THC or placebo)
Measured: 12 weeks
number of patients with migraine reduction greater than 50%
the number of patients with migraine reduction greater than 50% before and after the intervention (CBD+CBG+THC or placebo)
Measured: 12 weeks
number of patients with headache reduction greater than 50%
the number of patients with migraine reduction greater than 50% before and after the intervention (CBD+CBG+THC or placebo)
Measured: 12 weeks
Change in MIDAS score
the observed change in MIDAS score, before and after the intervention (CBD+CBG+THC or placebo)
Measured: 12 weeks
Change in HIT-6 score
the observed reduction in HIT-6 score, before and after the intervention (CBD+CBG+THC or placebo)
Measured: 12 weeks
Change in Beck's Anxiety Inventory scores
the observed change in BAI score, before and after the intervention (CBD+CBG+THC or placebo)
Measured: 12 weeks
Change in Beck's Depression Inventory scores
the observed change in BDI score, before and after the intervention (CBD+CBG+THC or placebo)
Measured: 12 weeks
Change in Severity of Dependence Scale scores
the observed change in SDS score, before and after the intervention (CBD+CBG+THC or placebo)
Measured: 12 weeks
Change in Epworth Sleepiness Scale scores
the observed change in Epworth score, before and after the intervention (CBD+CBG+THC or placebo)
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2021
- Study start18 Oct 2022
- Primary completion20 Feb 2025
- Study completion20 Feb 2025
Why it stopped: an interim analysis to rule out futility was positive, we completed active patients and stopped recruitment with 75 patients enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Migraine, HeadacheStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Israelita Albert Einstein
- Sponsor type
- University, hospital or other
- Collaborators
- Industria Farmacêutica Health Meds
- Responsible party
- Principal investigator, Alexandre Kaup, Hospital Israelita Albert Einstein
- Investigators
- Alexandre O Kaup, MD, PhD, Principal investigator, Clinical Research Hospital Israelita Albert Einstein, Neurologist
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04989413
- Sponsor's protocol ID
- HIAE CAMTREA Protocol
- Acronym
- CAMTREA
- Status last verified
- Feb 2025
- First submitted
- 24 May 2021
- Last updated
- 24 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double Blind Clinical Trial to Study the Effect of Cannabidiol (CBD) 133mg + Cannabigerol (CBG) 66mg + Tetrahydrocannabinol (THC) 4mg a Day As Adjunctive Therapy in the Treatment of Chronic Migraine - CAMTREA TRIAL
- ClinicalTrials.gov ID
- NCT04989413
- Acronym / sponsor ID
- CAMTREA / HIAE CAMTREA Protocol
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: an interim analysis to rule out futility was positive, we completed active patients and stopped recruitment with 75 patients enrolled
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Hospital Israelita Albert EinsteinUniversity, hospital or other
- Collaborators
- Industria Farmacêutica Health Meds
- Study start
- 18 Oct 2022 (actual)
- Primary completion
- 20 Feb 2025 (actual)
- Study completion
- 20 Feb 2025 (actual)
- First posted
- 4 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the effect of the cannabidiol (CBD) + cannabigerol (CBG) + tetrahydrocannabinol (THC) up to 133/66/4mg daily versus placebo as adjuvant treatment in chronic migraine (CM) patients under preventive treatment at a stable dose for at least 3 months who present at least 5 headaches day a month. CM patients of both sexes, between 25 and 65 years old, who have not had CBD and/or THC as a migraine treatment. Patients may be having migraine preventive treatment such as propranolol, atenolol, topiramate, valproic acid/sodium valproate, levetiracetam, gabapentin, lamotrigine, pre-gabaline, flunarizine, amitriptyline, nortriptyline, clomipramine, candesartan, galcanezumab, erenumab, fremanezumab, botulinum toxin type A. Acute treatment will follow patients doctor's prescription. Exclusion criteria: active liver disease or elevated liver transaminases> 3 times than the normal values, pregnancy, fertile age women without contraceptive treatment or who intend to get pregnant, patients without migraine preventive treatment or that changed the preventive treatment less than 3 months from the study start, substance abuse or addiction, use of medical cannabis or products with CBD or THC in the last 30 days or during study period, history of allergy or adverse reactions with the use of CBD or related products, substance users of liver enzymes inducers such as rifampicin, ketoconazole, theophylline, carbamazepine, phenytoin, phenobarbital and St. John's wort, clobazam, macrolides, verapamil, fluoxetine, amiodarone and tacrolimus. Patients on vitamin K anticoagulant medicines, as warfarin.
Randomization using a computacional system will stratify participants in each group by gender (F/M), age (25-34/35-44/45-54/55-65yo), headache days presented in the baseline month (5-10/11-15/16-20/21-25/26-30), overuse medication (yes or no). After randomization patients will be divided into two groups of 55 participants, who will receive CBD + CBG + THC up to a maximum daily dose of 133/66/4 mg or placebo for 12 weeks (V0 screening, V1 allocation, V4 final visit).
The main outcome is the reduction in frequency of headache days per 4 weeks between V1 and V4 compared to placebo. Secondary outcomes will be a reduction in duration and intensity of migraine attacks, amount of painkillers used and percentage of patients with a reduction greater than 50% on migraine days, 50% reduction in the other variables as MIDAS scores, HIT-6 scores, Beck's Anxiety and Depression Scales, Epworth Sleepiness Scales, and the scores at The Severity of Dependence Scale used as an indicator of overuse medication in this sample.
Clinical data will be registered on a personalized headache diary developed to this study using MyCap, from RedCap System, as an APP for daily entries using smartphones, androids or IOS system.
The clinical and laboratory data obtained in this study will comply with the objectives elaborated in the evaluation of the primary and secondary endpoints, the proposal of which is to publish the data regardless of the results obtained.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cannabidiol + Cannabigerol + Tetrahydrocannabinol 133/66/4mg | Active comparator | Drug: Cannabidiol + Cannabigerol + Tetrahydrocannabinol 133/66/4mgCannabidiol + Cannabigerol + Tetrahydrocannabinol in the maximum dosage of 133/66/4mg, divided in 2 doses of 66.5/33/2mg a day for 12 weeks. Each drop contain CBD/CBG/THC 1.66/0.8/0.05 mg, and medication will be titrated up as follow: day 1 to day 3 - 10 drops twice a day day 4 to day 6 - 20 drrops twice a day day 7 to day 9 - 30 drops twice a day from day 10 to the end of the study 40 drops twice a day |
| Placebo | Placebo comparator | Drug: Placebo oral dropsPlacebo capsules will be titrated up as follow: day 1 to day 3 - 10 drops twice a day day 4 to day 6 - 20 drops twice a day day 7 to day 9 - 30 drops twice a day from day 10 to the end of the study 40 drops twice a day |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients of both sexes, 25 to 65 years old, with chronic migraine according to IHS Classification System, 3rd edition
- Undergoing preventive treatment in a stable dose of the preventive medication for at least 2 months, who have not used cannabidiol to treat migraine.
- At least 5 days of migraine/migraine like attacks in the baseline period (4 weeks)
- As preventive drugs propranolol, atenolol, topiramate, valproic acid/sodium valproate, levetiracetam, gabapentin, lamotrigine, pre-gabaline, flunarizine, amitriptyline, nortriptyline, clomipramine, candesartan, galcanezumab, erenumab, fremanezumab, botulinum toxin type A will be allowed. Patients whose preventive treatment for migraine is Botulinum Toxin Type A may participate in the study as long as the toxin application interval used is 4 months (duration of medication or placebo use) and who have already received treatment with toxin at least 2 times.
- If acute treatment is necessary, patients may use the medications as previously advised by the physician accompanying them, and may use common, combined painkillers, anti-inflammatory drugs, triptans, triptans combined with anti-inflammatory drugs, opioid analgesics.
Key exclusion criteria (11 listed)
- Patients with active liver disease
- pregnancy and/or women who intend to become pregnant or who do not make adequate use of contraceptive therapy/methods
- breastfeeding women
- use of cannabis during the study, whether with therapeutic or recreational intentions
- patients who are without preventive treatment or who have undergone a dose change in preventive migraine treatment less than two months before V1 .
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo oral dropsuse of placebo for 12 weeks | Drug | Placebo |
| Cannabidiol + Cannabigerol + Tetrahydrocannabinol 133/66/4mguse of cannabidiol + canabigerol + thc for 12 weeks | Drug | Cannabidiol + Cannabigerol + Tetrahydrocannabinol 133/66/4mg |
Primary outcome
Migraine days
Time frame: 16 weeks
The primary outcome will be the reduction in migraine days observed between the baseline period (4 weeks before randomization) and the final visit 12 weeks of intervention (CBD+CBG+THC or placebo)
12 secondary outcomes
Headache days
Time frame: 12 weeks
migraine duration
Time frame: 12 weeks
migraine intensity
Time frame: 12 weeks
pain medicine intake
Time frame: 12 weeks
number of patients with migraine reduction greater than 50%
Time frame: 12 weeks
number of patients with headache reduction greater than 50%
Time frame: 12 weeks
Change in MIDAS score
Time frame: 12 weeks
Change in HIT-6 score
Time frame: 12 weeks
Change in Beck's Anxiety Inventory scores
Time frame: 12 weeks
Change in Beck's Depression Inventory scores
Time frame: 12 weeks
Change in Severity of Dependence Scale scores
Time frame: 12 weeks
Change in Epworth Sleepiness Scale scores
Time frame: 12 weeks
Results and safety
The study was stopped early (reason given: an interim analysis to rule out futility was positive, we completed active patients and stopped recruitment with 75 patients enrolled). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexandre O Kaup, MD, PhD principal investigator
Clinical Research Hospital Israelita Albert Einstein, Neurologist
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Cannabidiol + Cannabigerol + Tetrahydrocannabinol 133/66/4mg in people with Chronic Migraine, Headache and Overuse Headache Medication, run by Hospital Israelita Albert Einstein at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: an interim analysis to rule out futility was positive, we completed active patients and stopped recruitment with 75 patients enrolled). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Migraine days (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2025.