Cannabis Oil for Pain in Parkinson's Disease

NCT03639064 | Unknown Phase 2

• 1 other identifier: 17-6086.0
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

Full Title: A phase II, randomized, open-label, double-blind, two-center study to evaluate the tolerability, safety and dose-finding of oil cannabis preparation for pain in Parkinson's disease. Short title: Cannabis oil for pain in Parkinson's disease Sample Size: N = 15 Study Population: Patients with Parkinson's disease and pain, without cognitive impairment. Study Duration: July 2018 - July 2019 Study Agent/ Intervention: Cannabis oil: mixed oil cannabis preparation consisting of 3 different formulations of ∆-9THC and cannabidiol - 18:0; 10:10; and 1:20 respectively. Cannabis oil will be administered orally once per day, as required for pain; or taken 4h before bedtime, if no pain. Primary objective: to determine the safety and tolerability of different formulations of Cannabis oil for pain in PD patients (incidence and severity of adverse events). Secondary objective: to assess change from the start of treatment (V2) to end of treatment (V5) in frequency and severity of pain, sleep, dystonia and motor symptoms in PD patients.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) in each individual

  MTD will be defined as the dose of each CanniMed® preparation for which the subject was able to be on for a minimum of 1 week, without the occurrence of an AE or suspected AE, with the severity grading of 2 or higher (CTCAE v.4.0)

  From baseline (Visit 1) to end of study (Visit 5); total 35 days of intervention.

• Treatment-emergent adverse events (safety)

  Determine the incidence and severity of adverse events by direct patient questioning, physical examination and ancillary testing as per protocol

  From baseline (Visit 1) to end of study (Visit 5); total 35 days of intervention.

Secondary Outcomes (1)

• Collect the King's Parkinson Disease Pain scale (KPPS) scores in the intervention group, adjusted for baseline scores.

  From baseline (Visit 1) to Follow-up phone call (1 week after Visit 5); Total 35 days

Other Outcomes (5)

• Changes in the Visual Analogue Scale for Pain (adjusted for baseline scores)

  From baseline (Visit 1) to end of study (Visit 5); total 35 days.

• Changes in the MDS-UPDRS part III (adjusted for baseline scores)

  From baseline (Visit 1) to end of study (Visit 5); total 35 days.

• Changes in the UDysRS - Dystonia part 2 subscores (adjusted for baseline)

  From baseline (Visit 1) to end of study (Visit 5); total 35 days.

Study Arms (3)

CanniMed® Oil 1:20 formulation

EXPERIMENTAL

∆9-THC: 1.0 mg/mL; CBD: 20.0 mg/mL

Drug: Cannabis Oil

CanniMed® Oil 10:10 formulation

EXPERIMENTAL

∆9-THC: 9.8 mg/mL; CBD: 9.9 mg/mL

Drug: Cannabis Oil

CanniMed® Oil 18:0 formulation

EXPERIMENTAL

∆9-THC: 18.3 mg/mL; CBD: 0.2 mg/mL

Drug: Cannabis Oil

Interventions

Cannabis Oil DRUG

Mixed oil cannabis preparation consisting of 3 differing formulations of ∆-9THC and CBD is clinically available in Canada as CanniMed®. The 3 differing formulations of CanniMed® oils contain varying proportions of ∆-9THC and CBD in the following ratios: 18:0; 10:10; 1:20. All CanniMed® oil formulations consist of cannabinoids extracted from dried cannabis, and diluted in olive oil.

CanniMed® Oil 10:10 formulation; CanniMed® Oil 18:0 formulation; CanniMed® Oil 1:20 formulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects;
• Aged \>18y
• International Parkinson and Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson Disease.
• Bothersome Pain - Defined as Severity score of 2 or more (Moderate pain of some distress to the patient); and Frequency score of 2 or more (at least 1 episode/week) in at least one pain domain according to King's Parkinson Disease Pain Scale (KPPS, see supplements);
• On stable PD medications in the month prior to enrollment.
• Drugs used to treat pain, including dopaminergic drugs, analgesics, non-steroidal anti-inflammatories and opiates will be allowed to be continued during the study period but doses must be unchanged.
• Women of childbearing age must be non-pregnant and using a reliable method of contraception and have a negative pregnancy test at screening. Acceptable methods of contraception include using oral injected or implanted methods of hormonal contraceptives for at least 3 months prior to randomization and the partner should also use a barrier method (e.g. condom) with spermicidal foam/gel/film/cream/suppository during this study. Additional pregnancy testing will be completed if necessary throughout the study duration.
• Subject agrees not to drive for the duration of the study.

You may not qualify if:

• Secondary parkinsonism (as per MDS Diagnostic Criteria).
• Previous serious adverse event or hypersensitivity to cannabis or cannabinoids
• Current use of cannabinoids or marijuana within 90 days prior to screening.
• Cognitive impairment or dementia (Montreal Cognitive Assessment/MoCA \< 24).
• Current substance use disorder according to the Diagnostic and Statistical Manual of Mental Disorder Fifth Edition (DSM-5) and lifetime history of dependence on cannabis or diagnosis of cannabis use disorder (CUD) according to the DSM-5
• History of clinically significant impulse control disorders: QUIP-RS- part A-D ≥ 10 and part E ≥ 7.
• Current suicidal ideation within one year prior to the second Screening Visit as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the C-SSRS or attempted suicide within the last 5 years.
• Symptomatic orthostatic hypotension or drop in (standing from sitting) blood pressure of \>20 mmHg (systolic) and \>10 mmHg (diastolic).
• Significant hepatic disease (AST, ALT, ALP \>2xUpper Normal Limit).
• Normal renal function (defined as serum creatinine level \<133 µmol/L and Estimated Glomerular Filtration Rate (eGFR) greater than or equal to 60)
• Uncontrolled and severe cardiovascular disease, as per clinical judgment.
• History of problematic substance abuse, or substance use disorder, whether of alcohol, prescription drugs or illicit drugs
• Other contra-indication as per Health Canada recommendation for use of cannabis - see reference 21.
• Inability or unwillingness of subject to give written informed consent.
• Participation in another investigational study at the time of recruitment or during the prior month.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Parkinson Society Canada: collaborator

Study Sites (2)

Parkinson's Disease and Movement Disorders Clinic - Ottawa Hospital Research Institute

Ottawa, Ontario, K1Y 4E9, Canada

NOT YET RECRUITING

Movement Disorders Clinic, Toronto Western Hospital, 399, Bathurst St

Toronto, Ontario, M5V 2T8, Canada

RECRUITING

Related Publications (8)

• Negre-Pages L, Regragui W, Bouhassira D, Grandjean H, Rascol O; DoPaMiP Study Group. Chronic pain in Parkinson's disease: the cross-sectional French DoPaMiP survey. Mov Disord. 2008 Jul 30;23(10):1361-9. doi: 10.1002/mds.22142.

  PMID: 18546344 RESULT

• Ha AD, Jankovic J. Pain in Parkinson's disease. Mov Disord. 2012 Apr;27(4):485-91. doi: 10.1002/mds.23959. Epub 2011 Sep 23.

  PMID: 21953990 RESULT

• More SV, Choi DK. Promising cannabinoid-based therapies for Parkinson's disease: motor symptoms to neuroprotection. Mol Neurodegener. 2015 Apr 8;10:17. doi: 10.1186/s13024-015-0012-0.

  PMID: 25888232 RESULT

• Fox SH, Henry B, Hill M, Crossman A, Brotchie J. Stimulation of cannabinoid receptors reduces levodopa-induced dyskinesia in the MPTP-lesioned nonhuman primate model of Parkinson's disease. Mov Disord. 2002 Nov;17(6):1180-7. doi: 10.1002/mds.10289.

  PMID: 12465055 RESULT

• Engler B, Freiman I, Urbanski M, Szabo B. Effects of exogenous and endogenous cannabinoids on GABAergic neurotransmission between the caudate-putamen and the globus pallidus in the mouse. J Pharmacol Exp Ther. 2006 Feb;316(2):608-17. doi: 10.1124/jpet.105.092718. Epub 2005 Oct 7.

  PMID: 16214880 RESULT

• Lynch ME, Ware MA. Cannabinoids for the Treatment of Chronic Non-Cancer Pain: An Updated Systematic Review of Randomized Controlled Trials. J Neuroimmune Pharmacol. 2015 Jun;10(2):293-301. doi: 10.1007/s11481-015-9600-6. Epub 2015 Mar 22.

  PMID: 25796592 RESULT

• Kluger B, Triolo P, Jones W, Jankovic J. The therapeutic potential of cannabinoids for movement disorders. Mov Disord. 2015 Mar;30(3):313-27. doi: 10.1002/mds.26142. Epub 2015 Feb 4.

  PMID: 25649017 RESULT

• Koppel BS, Brust JC, Fife T, Bronstein J, Youssof S, Gronseth G, Gloss D. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders [RETIRED]: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014 Apr 29;82(17):1556-63. doi: 10.1212/WNL.0000000000000363.

  PMID: 24778283 RESULT

Related Links

• HealthCanada. Information for Health Care Professionals. Cannabis (marihuana, marijuana) and the cannabinoids

MeSH Terms

Conditions

Parkinson Disease

Interventions

nabiximols

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Susan Fox, MD, PhD

  UHN - Toronto Western Hospital - 399 Bathurst Street, McLaughlin pavilion, 7th Floor Toronto, ON, M5T 2S8 - Canada

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Susan Fox, MD, PhD

CONTACT

416-699-9837; sfox@uhnresearch.ca

Carlos Ropa, Coordinator

CONTACT

416-603-5800; Carlos.Ropa@uhnresearch.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This will be a double-blind study. The different cannabis oil formulations have the same colour, taste and smell. Study investigators will be blind to the dose/formulation of cannabis oil. Unblinding will only be performed in the event of a Serious AE. The site PI will maintain a randomization list kept in a locked secure 24h a day accessible location for emergency unblinding.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an interventional, phase II, randomized, open-label, double-blind, two-centre study to evaluate the safety, tolerability, and dose-finding of Cannabis oil preparation for pain in Parkinson's disease. Mixed oil cannabis preparation consisting of 3 differing formulations of ∆-9THC and CBD is clinically available in Canada as CanniMed®. The 3 differing formulations of CanniMed® oils contain varying proportions of ∆-9THC and CBD in the following ratios: 18:0; 10:10; 1:20. A total of 15 patients will be block randomized to one of the three groups. Each patient will receive one formulation of CanniMed® Oil only, with 5 patients per group.

Study Record Dates

• First Submitted: July 4, 2018
• First Posted: August 20, 2018
• Study Start: December 1, 2020
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: March 10, 2022

Record last verified: 2021-11

Locations

CA (2)