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Cannabidiol 133mg + Cannabigerol 66mg + Tetrahydrocannabinol 4mg vs Placebo as Adjuvant Treatment in Chronic Migraine - (CAMTREA)

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ClinicalTrials.gov Identifier: NCT04989413
Recruitment Status : Not yet recruiting
First Posted : August 4, 2021
Last Update Posted : August 4, 2021
Sponsor:
Collaborator:
Industria Farmacêutica Health Meds
Information provided by (Responsible Party):
Alexandre Kaup, Hospital Israelita Albert Einstein

Brief 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. 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, topiramate, valproic acid/sodium valproate, flunarizine, amitriptyline, nortriptyline, 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, 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. Patients on vitamin K anticoagulant medicines, as warfarin. After randomization patients will be divided into two groups of 55 participants, who will receive CBD + CBG + THC up to a maximum 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.

The clinical and laboratory data obtained in this study will comply with the objectives elaborated in the evaluation of the primary and secondary, the proposal of which is to publish the data regardless of the results obtained.


Condition or disease Intervention/treatment Phase
Chronic Migraine, Headache Overuse Headache Medication Drug: Placebo oral drops Drug: Cannabidiol + Cannabigerol + Tetrahydrocannabinol 133/66/4mg Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double Blind Clinical Trial to Study the Effect of Cannabidiol (CBD) 133mg + Cannabigerol 66mg + Tetrahydrocannabinol (THC) 4mg a Day as Adjunctive Therapy in the Treatment of Chronic Migraine - CAMTREA TRIAL
Estimated Study Start Date : August 2, 2021
Estimated Primary Completion Date : July 18, 2022
Estimated Study Completion Date : December 19, 2022

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Migraine
MedlinePlus related topics: Headache Migraine

Arm Intervention/treatment
Active Comparator: Cannabidiol + Cannabigerol + Tetrahydrocannabinol 133/66/4mg
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
Drug: Cannabidiol + Cannabigerol + Tetrahydrocannabinol 133/66/4mg
use of cannabidiol + canabigerol + thc for 12 weeks

Placebo Comparator: Placebo

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

Drug: Placebo oral drops
use of placebo for 12 weeks




Primary Outcome Measures :
  1. Migraine days [ Time Frame: 16 weeks ]
    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 (cannabidiol plus tetrahydrocannabinol or placebo)


Secondary Outcome Measures :
  1. migraine duration [ Time Frame: 12 weeks ]
    the attack duration in hours observed before and after the intervention (CBD+CBG+THC or placebo)

  2. migraine intensity [ Time Frame: 12 weeks ]
    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)

  3. pain medicine intake [ Time Frame: 12 weeks ]
    the amount of pain medicine intake as needed before and after the intervention (CBD+CBG+THC or placebo)

  4. number of patients with migraine reduction greater than 50% [ Time Frame: 12 weeks ]
    the number of patients with migraine reduction greater than 50% before and after the intervention (CBD+CBG+THC or placebo)

  5. Change in MIDAS score [ Time Frame: 12 weeks ]
    the observed change in MIDAS score, before and after the intervention (CBD+CBG+THC or placebo)

  6. Change in HIT-6 score [ Time Frame: 12 weeks ]
    the observed reduction in HIT-6 score, before and after the intervention (CBD+CBG+THC or placebo)

  7. Change in Beck's Anxiety Inventory scores [ Time Frame: 12 weeks ]
    the observed change in BAI score, before and after the intervention (CBD+CBG+THC or placebo)

  8. Change in Beck's Depression Inventory scores [ Time Frame: 12 weeks ]
    the observed change in BDI score, before and after the intervention (CBD+CBG+THC or placebo)

  9. Change in Severity of Dependence Scale scores [ Time Frame: 12 weeks ]
    the observed change in SDS score, before and after the intervention (CBD+CBG+THC or placebo)

  10. Change in Epworth Sleepiness Scale scores [ Time Frame: 12 weeks ]
    the observed change in Epworth score, before and after the intervention (CBD+CBG+THC or placebo)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   25 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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, topiramate, valproic acid/sodium valproate, flunarizine, amitriptyline, nortriptyline 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.

Exclusion Criteria:

  • 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.
  • History of substance abuse or addiction, use of medical cannabis or products with CBD 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. -
  • Patients using anticoagulants.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04989413


Contacts
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Contact: Fernanda Assir +55 11 21510724 fernanda.assir@einstein.br

Sponsors and Collaborators
Hospital Israelita Albert Einstein
Industria Farmacêutica Health Meds
Investigators
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Principal Investigator: Alexandre O Kaup, MD, PhD Clinical Research Hospital Israelita Albert Einstein, Neurologist
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Responsible Party: Alexandre Kaup, Principal Investigator, MD, Hospital Israelita Albert Einstein
ClinicalTrials.gov Identifier: NCT04989413    
Other Study ID Numbers: HIAE CAMTREA Protocol
First Posted: August 4, 2021    Key Record Dates
Last Update Posted: August 4, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Migraine Disorders
Headache
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Pain
Neurologic Manifestations
Dronabinol
Cannabidiol
Anticonvulsants
Hallucinogens
Physiological Effects of Drugs
Psychotropic Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Cannabinoid Receptor Agonists
Cannabinoid Receptor Modulators
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists