Clinical trial NCT04398446: Effect of Hemp-CBD on Patients With CIPN
Official title: Coala-T-CBD Study: A Study of the Effect of Hemp-CBD on the Severity and Duration of Chemotherapy-Induced Peripheral Neuropathy in Patients Receiving Neurotoxic Chemotherapy for Non-Metastatic Breast, Uterine, Pancreatic, and Colorectal Cancer and All Stages of Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Chemotherapy-induced Peripheral Neuropathy
Colorectal Cancer Stage II
Colorectal Cancer Stage III
Breast Cancer
Ovarian Cancer
Uterine Cancer
Pancreatic Cancer
Lead sponsor: Main Line Health
Sponsor class: OTHER
Collaborators: name: Ananda Hemp, Inc.
First posted: 2020-05-21
Enrollment: 56
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the effect of a hemp-based cannabidiol (CBD) product, Ananda Hemp Spectrum Gelcaps, on the severity and duration of chemotherapy-induced neuropathy (CIPN) among non-metastatic breast, uterine, pancreatic, and colorectal cancer, and all stages of ovarian cancer in patients who received neoadjuvant or adjuvant therapy that included neurotoxic chemotherapeutic agents.

Detailed description: CIPN is a common complication of many effective cytotoxic agents that can negatively impact patients' treatment course and quality of life. The incidence of CIPN in cancer patients receiving multidrug regimens is estimated at 38%, with frequencies approaching 100% with certain known neurotoxic drug classes. Taxanes (e.g., paclitaxel, docetaxel) and platinum-based agents (e.g., oxaliplatin, cisplatin, carboplatin) in particular, are two commonly used chemotherapy classes that are associated with a high incidence of CIPN. Symptoms of chemotherapy-induced peripheral neuropathy include distal extremity numbness, tingling and pain. Chronic, cumulative symptoms can severely impact quality of life and result in dose reductions and/or drug discontinuation in up to 30% of patients.

Consumers use cannabis products for various reasons including pain, stress, anxiety, and insomnia. The neuro-modulatory effects of phytocannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD) in particular, have been documented at both the molecular and clinical level. The endocannabinoid system consists of CB1 receptors and CB2 receptors that act as an inhibitory G-protein within the central and peripheral nervous system, respectively. Several animal models have demonstrated the role endocannabinoids play in neuropathic pain development by showing enhanced neuropathic pain with CB1 receptor deletion and reduced manifestations of neuropathic pain with CB2 receptor overexpression. The therapeutic properties of cannabis-based products have also been illustrated in several randomized double-blind trials that have shown significant pain relief versus placebo in the treatment of neuropathy related to diabetes, spinal cord injury, multiple sclerosis, and HIV associated polyneuropathy. Studies specifically looking at the role of CBD in chemotherapy-induced neurotoxicity have shown a neuroprotective effect of CBD in mouse models. Studies have demonstrated that a 14-day dosing regimen of CBD prevented the onset of paclitaxel-induced mechanical and thermal sensitivity.

These intriguing results suggest that cannabinoid agents could potentially reduce the severity and duration of CIPN in the clinical setting.

Eligibility criteria: Inclusion Criteria:

* Non-metastatic breast cancer patients who developed CIPN (CTCAE sensory grade 2 or 3, motor grade \<2) after receiving taxane-based chemotherapy in pre-operative or post-operative setting.
* Non-metastatic Colorectal cancer patients with high risk stage II and stage III disease who developed CIPN (CTCAE sensory grade 2 or 3, motor grade \<2) after receiving oxaliplatin in the adjuvant setting.
* Ovarian cancer patients who developed CIPN (CTCAE sensory grade 2 or 3, motor grade \<2) after receiving taxane-containing chemotherapy in the neoadjuvant or adjuvant setting .
* Uterine cancer patients who developed CIPN (CTCAE grade 2 or 3) after receiving taxane-containing chemotherapy in the neoadjuvant or adjuvant setting.
* Non-metastatic pancreatic cancer patients who developed CIPN (CTCAE grade 2 or 3) after receiving taxane-containing chemotherapy in the neoadjuvant or adjuvant setting.

Exclusion Criteria:

* Family history of genetic/familial neuropathy
* Routine use of recreational or medicinal marijuana products (defined as \> 4 times per month) or illicit drug use (positive urine drug screen including opioids, cocaine, amphetamines, PCP, LSD)
* Known underlying liver disease (Child-Pugh B or C) or baseline elevation in ALT, AST or total bilirubin ≥1.5 x upper limit of normal
* Patients taking certain medications will be excluded due to potential CBD-drug interaction. CBD may prevent appropriate drug metabolism increasing risk for toxicity. Co-administration of study product and the following medications will be contraindicated and may lead to participant exclusion: clarithromycin, itraconazole, erythromycin, fluconazole, clopidogrel, rifampin, sulfamethoxazole, warfarin, any opioids, warfarin, antiepileptic medications (including carbamazapine, phenytoin, valproic acid, but excepting of gabapentin, clonazepam or diazepam).
* Underlying history of epilepsy/ recurrent seizure disorder or unexplained seizure within past 6 months
* Patients with uncontrolled cardiovascular disease defined by myocardial infarction, stroke or transient ischemic attack, or need for coronary stent placement within past six months.
* Patients with uncontrolled psychiatric illness (who meet DSM-V criteria) or who are at increased risk for suicidality based on baseline Columbia-Suicide Severity Rating Scale.
* Women who are pregnant or breastfeeding or who refuse to practice an effective form of birth control (condoms, diaphragm, birth control pill, IUD)

Primary outcomes:
measure: Change in pressure/touch sensation during intervention and at follow-up
timeFrame: Every two weeks for twelve weeks during intervention; One month follow-up
measure: Change in pain sensation during intervention and at follow-up
timeFrame: Every two weeks for twelve weeks during intervention; One month follow-up
measure: Change in vibration sensation during intervention and at follow-up
timeFrame: Every two weeks for twelve weeks during intervention; One month follow-up
measure: Change in quality of life
timeFrame: Every two weeks for twelve weeks during intervention; One month follow-up
measure: Change in CIPN symptom severity
timeFrame: Every two weeks for twelve weeks during intervention; One month follow-up
measure: Change in pain severity
timeFrame: Every two weeks for twelve weeks during intervention; One month follow-up
measure: Change in sleep quality
timeFrame: Every two weeks for twelve weeks during intervention; One month follow-up
Secondary outcomes:
measure: Receptivity and accrual rate to clinical studies involving cannabis-based substances.
timeFrame: 1 Day
measure: Adherence to CBD Products
timeFrame: Daily, 12 weeks
measure: Rate of side effects using medical-grade CBD concentrates
timeFrame: Daily, 12 weeks
Other outcomes:
Locations:
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
Study officials:
affiliation: Main Line Health System
name: Marisa Weiss, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lee G, Grovey B, Furnish T, Wallace M. Medical Cannabis for Neuropathic Pain. Curr Pain Headache Rep. 2018 Feb 1;22(1):8. doi: 10.1007/s11916-018-0658-8.
citation: Brzezinski K. Chemotherapy-induced polyneuropathy. Part I. Pathophysiology. Contemp Oncol (Pozn). 2012;16(1):72-8. doi: 10.5114/wo.2012.27341. Epub 2012 Feb 29.
citation: Brzezinski K. Chemotherapy-induced peripheral neuropathy. Part II. Prevention. Contemp Oncol (Pozn). 2012;16(3):258-61. doi: 10.5114/wo.2012.29296. Epub 2012 Jul 6.
citation: Saif MW, Reardon J. Management of oxaliplatin-induced peripheral neuropathy. Ther Clin Risk Manag. 2005 Dec;1(4):249-58.
citation: Wang WS, Lin JK, Lin TC, Chen WS, Jiang JK, Wang HS, Chiou TJ, Liu JH, Yen CC, Chen PM. Oral glutamine is effective for preventing oxaliplatin-induced neuropathy in colorectal cancer patients. Oncologist. 2007 Mar;12(3):312-9. doi: 10.1634/theoncologist.12-3-312.
citation: Ward SJ, Ramirez MD, Neelakantan H, Walker EA. Cannabidiol prevents the development of cold and mechanical allodynia in paclitaxel-treated female C57Bl6 mice. Anesth Analg. 2011 Oct;113(4):947-50. doi: 10.1213/ANE.0b013e3182283486. Epub 2011 Jul 7.