The Kinetics of Endocannabinoids in Patients With Chemotherapy Induced Peripheral Neuropathy by Using Medical Cannabis.

Chemotherapy-induced Peripheral Neuropathy Clinical Trial

Official title:

The Kinetics of Endocannabinoids in Patients With Chemotherapy Induced Peripheral Neuropathy by Using a Portable Metered-Dose Cannabis Inhaler

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04376437
• Other study ID #: ENDO-CIPN 1
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 15, 2022
• Est. completion date: December 1, 2023

Study information

• Verified date: March 2022
• Source: HaEmek Medical Center, Israel
• Contact: Gil Bar Sela, Prof
• Phone: +97250-206-1207
• Email: gil_ba[@]clalit.org.il
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Chemotherapy-induced peripheral neuropathy (CIPN) is the most common neurological cancer treatment complication. Medical cannabis is indicated in Israel for the treatment of chronic pain, spasticity and for the control of pain and other symptoms in patients with cancer. The proposed study aims are to study about the changes in level of endocannabinoids following continuous exposure to phytocannabinoids and about the long-term effect of medical cannabis on CIPN.

Description:

This will be a self-titrated, open-label design study. Subjects who begin taxanes or oxaliplatine therapy and were diagnosed with CIPN will be recruited to the study. After providing their written informed consent, the study physician obtained a medical history, demographic details and conducted a physical examination. During the current study, baseline period for CIPN evaluation will be 2 weeks, while patients will fill several questionnaires. Baseline CIPN will be evaluating by DN4 and BPI questionnaires. EQ-5D and PSQI will be filled for baseline Quality of life (QOL) and sleepiness status, accordingly.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: December 1, 2023
• Est. primary completion date: December 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 1. Age above 18 years and below 80 years old. 2. Pathology of Breast or GI malignancies. 3. Treatment with Taxans (Taxol/ Taxotere) or Oxaliplatin for adjuvant treatment or metastatic disease.

4. Estimated life expectancy = 6 months. 5. Performance status =1 (ECOG classification). 6. Sign of written informed consent. 7. CIPN is examined during the chemotherapy treatment DN4 score must be above 4 (and by physician decision) for more than one week.

8. Patient with adequate liver/renal function at screening as described:

• Creatinine clearance >30 ml/min as calculated by Cockcroft-Gault Equation.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 x ULN.

9. Patients who suffer from pain although using a stable analgesic treatment' at least 14 days before entering the trial (no limitation for the use of the analgesic).

10. Patient possessed a valid license from the Israeli Ministry of Health to receive medicinal cannabis.

11. Patient is able and willing to comply with study requirements. 12. Patient agrees to use only medical cannabis provided by study team until the end of study period.

13. Patient has not undergone major surgery in the month prior to the study start.

14. Patient agrees not to participate in other interventional clinical trial during the study participation.

Exclusion Criteria:

• 1. Use of cannabis or synthetic cannabinoids in the last two weeks (urine test for cannabinoids are positive).

2. Patient with known or past substance abuse. 3. Patients with major psychiatric disorders (e.g. schizophrenia, dementia, and intellectual disabilities).

4. Patients with first degree siblings under the age of 30 years old with psychiatric disorders.

5. Patients with uncontrolled diabetes mellitus, cardiovascular, or convulsive disorders according to investigator.

6. Patients with sensitivity to cannabis or cannabinoids. 7. Patients with known neuropathic pain due to diabetes or other diseases. 8. Patients with severe respiratory disease. 9. Patients with brain metastases or brain tumors may participate if completed radiotherapy treatment at least 14 days prior to signing the informed consent and last imaging did not show any worsening.

10. Female subjects who are pregnant, lactating, or want to get pregnant during the study period and one month following the study. Male subjects who want their partner to get pregnant during the study period and one month following the study.

11. Females of childbearing potential or males whose partners with childbearing potential and did not use adequate contraceptives 28 days prior to study start or during the study.

12. Other life-threatening medical conditions that disqualify the patient from participating in the study, according to the Primary Investigator's judgment.

13. Anticipated alcohol or barbiturate use during the study period. 14. Participation in other clinical trials during the last month. 15. Subjects who are using one of the following medications: opiates (Primidone, Phenobarbitol, Arbamazepine, Rifampicin, Rifabutin, Troglitazone and Hypericum perforatum).

16. Patient who has undergone a major surgery a month prior to study start.

Related Conditions & MeSH terms

• Chemotherapy-induced Peripheral Neuropathy
• Peripheral Nervous System Diseases

Intervention

Drug:
• medical cannabis
inhalation by using a Portable Metered-Dose Cannabis Inhaler

Locations

Country	Name	City	State
Israel	Haemek MC	Afula	North

Sponsors (3)

Lead Sponsor	Collaborator
HaEmek Medical Center, Israel	Syqe Medical, Technion, Israel Institute of Technology

Country where clinical trial is conducted

Israel, 

References & Publications (20)

Abrams DI, Jay CA, Shade SB, Vizoso H, Reda H, Press S, Kelly ME, Rowbotham MC, Petersen KL. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology. 2007 Feb 13;68(7):515-21. — View Citation

Andreae MH, Carter GM, Shaparin N, Suslov K, Ellis RJ, Ware MA, Abrams DI, Prasad H, Wilsey B, Indyk D, Johnson M, Sacks HS. Inhaled Cannabis for Chronic Neuropathic Pain: A Meta-analysis of Individual Patient Data. J Pain. 2015 Dec;16(12):1221-1232. doi: — View Citation

Berman P, Futoran K, Lewitus GM, Mukha D, Benami M, Shlomi T, Meiri D. A new ESI-LC/MS approach for comprehensive metabolic profiling of phytocannabinoids in Cannabis. Sci Rep. 2018 Sep 24;8(1):14280. doi: 10.1038/s41598-018-32651-4. — View Citation

Boychuk DG, Goddard G, Mauro G, Orellana MF. The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review. J Oral Facial Pain Headache. 2015 Winter;29(1):7-14. doi: 10.11607/ofph.1274. Review. — View Citation

Eisenberg E, Ogintz M, Almog S. The pharmacokinetics, efficacy, safety, and ease of use of a novel portable metered-dose cannabis inhaler in patients with chronic neuropathic pain: a phase 1a study. J Pain Palliat Care Pharmacother. 2014 Sep;28(3):216-25. — View Citation

Ellis RJ, Toperoff W, Vaida F, van den Brande G, Gonzales J, Gouaux B, Bentley H, Atkinson JH. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology. 2009 Feb;34(3):672-80. doi: 10.1038/npp. — View Citation

Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet. 2003;42(4):327-60. Review. — View Citation

Hammack JE, Michalak JC, Loprinzi CL, Sloan JA, Novotny PJ, Soori GS, Tirona MT, Rowland KM Jr, Stella PJ, Johnson JA. Phase III evaluation of nortriptyline for alleviation of symptoms of cis-platinum-induced peripheral neuropathy. Pain. 2002 Jul;98(1-2): — View Citation

Jhaveri MD, Sagar DR, Elmes SJ, Kendall DA, Chapman V. Cannabinoid CB2 receptor-mediated anti-nociception in models of acute and chronic pain. Mol Neurobiol. 2007 Aug;36(1):26-35. Epub 2007 Oct 2. Review. — View Citation

La Porta C, Bura SA, Llorente-Onaindia J, Pastor A, Navarrete F, García-Gutiérrez MS, De la Torre R, Manzanares J, Monfort J, Maldonado R. Role of the endocannabinoid system in the emotional manifestations of osteoarthritis pain. Pain. 2015 Oct;156(10):20 — View Citation

Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br J Clin Pharmacol. 2011 Nov;72(5):735-44. doi: 10.1111/j.1365-2125.2011.03970.x. Review. — View Citation

Mitchell PL, Goldstein D, Michael M, Beale P, Friedlander M, Zalcberg J, White S, Thomson JA, Clarke S. Addition of gabapentin to a modified FOLFOX regimen does not reduce oxaliplatin-induced neurotoxicity. Clin Colorectal Cancer. 2006 Jul;6(2):146-51. — View Citation

Pachman DR, Watson JC, Loprinzi CL. Therapeutic strategies for cancer treatment related peripheral neuropathies. Curr Treat Options Oncol. 2014 Dec;15(4):567-80. doi: 10.1007/s11864-014-0303-7. Review. — View Citation

Pascual D, Goicoechea C, Suardíaz M, Martín MI. A cannabinoid agonist, WIN 55,212-2, reduces neuropathic nociception induced by paclitaxel in rats. Pain. 2005 Nov;118(1-2):23-34. Epub 2005 Oct 4. — View Citation

Rahn EJ, Makriyannis A, Hohmann AG. Activation of cannabinoid CB1 and CB2 receptors suppresses neuropathic nociception evoked by the chemotherapeutic agent vincristine in rats. Br J Pharmacol. 2007 Nov;152(5):765-77. Epub 2007 Jun 18. — View Citation

Rao RD, Flynn PJ, Sloan JA, Wong GY, Novotny P, Johnson DB, Gross HM, Renno SI, Nashawaty M, Loprinzi CL. Efficacy of lamotrigine in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled trial — View Citation

Skrabek RQ, Galimova L, Ethans K, Perry D. Nabilone for the treatment of pain in fibromyalgia. J Pain. 2008 Feb;9(2):164-73. Epub 2007 Nov 5. — View Citation

Vulfsons S, Ognitz M, Bar-Sela G, Raz-Pasteur A, Eisenberg E. Cannabis treatment in hospitalized patients using the SYQE inhaler: Results of a pilot open-label study. Palliat Support Care. 2020 Feb;18(1):12-17. doi: 10.1017/S147895151900021X. — View Citation

Ware MA, Wang T, Shapiro S, Robinson A, Ducruet T, Huynh T, Gamsa A, Bennett GJ, Collet JP. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ. 2010 Oct 5;182(14):E694-701. doi: 10.1503/cmaj.091414. Epub 2010 Aug 30. — View Citation

Zusman SP, Lustig JP, Bin Nun G. Cost evaluation of two methods of post tooth extraction hemostasis in patients on anticoagulant therapy. Community Dent Health. 1993 Jun;10(2):167-73. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in the level of 150 different endocannabinoids.	Circulating endocannabinoids concentrations .	Determined on blood samples collected during the 4 months of participation in the study
Secondary	Changes from the baseline of neuropathic pain during medical cannabis treatment .	Neuropathic pain detected by DN4 questionnaire .	during 4 months of participation in the study
Secondary	Changes in Quality of life by FACT-GOG-Ntx	Changes of Quality of life will be evaluated by Functional Assessment of Cancer Therapy - Gynecologic Oncology Group-Neurotoxicity ( FACT-GOG-Ntx) questionnaire	This exam will be performed every visit.during 4 months of participation in the study
Secondary	Changes in Quality of life by BPI	Changes of Quality of life will be evaluated by BRIEF PAIN INVENTORY (BPI) tool.	This exam will be performed every visit.during 4 months of participation in the study