Effect of Hemp-CBD on Patients With CIPN (Coala-T-CBD)
Primary Purpose
Chemotherapy-induced Peripheral Neuropathy, Colorectal Cancer Stage II, Colorectal Cancer Stage III
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Hemp-based CBD
Placebo oral tablet
Sponsored by
About this trial
This is an interventional treatment trial for Chemotherapy-induced Peripheral Neuropathy
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)
Sites / Locations
- Lankenau Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Hemp-based CBD
Placebo Oral Tablet
Arm Description
Outcomes
Primary Outcome Measures
Change in pressure/touch sensation during intervention and at follow-up
At regular intervals, CIPN will be assessed by Semmes Weinstein Monofilament Examination using Touch-Test Sensory Evaluator Kit to determine pressure sensation.
Change in pain sensation during intervention and at follow-up
At regular intervals, CIPN will be assessed by pinprick examination to determine pain sensation.
Change in vibration sensation during intervention and at follow-up
At regular intervals, CIPN will be assessed by 128Hz tuning fork vibration test to determine vibration sensation.
Change in quality of life
Quality of life will be measured by European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire, a validated 30-item questionnaire to assess treatment impact on quality of life in cancer patients on 4-point scales, where 4 is most severe.
Change in CIPN symptom severity
CIPN symptoms will be measured by EORTC QLQ-CIPN20 Questionnaire, validated 20-item questionnaire to assess symptom severity of chemotherapy-induced peripheral neuropathy on 4-point scales, where 4 is most severe.
Change in pain severity
Pain severity will be measured by Brief Pain Inventory (BPI) Short Form, validated 9-item questionnaire to assess the severity of pain and the impact of pain on daily functions on 10-point scales, where 10 is most severe.
Change in sleep quality
Sleep quality will be measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Questionnaire, validated 8-item questionnaire to assess sleep quality on 5-point scales, where 5 is the most severe.
Secondary Outcome Measures
Receptivity and accrual rate to clinical studies involving cannabis-based substances.
Receptivity to clinical trials as well as to the use of CBD will be assessed using a questionnaire that will be distributed to all patients at the first encounter. Responses to this questionnaire will provide information regarding in the use of CBD was influencing factor for those who chose to participate or deferring factor for those who decline participation.
Adherence to CBD Products
Adherence will be assessed with a Dosing Diary.
Rate of side effects using medical-grade CBD concentrates
Side effects will be assessed at each encounter clinical evaluation by patient report in a Dosing Diary. All side effects thought to be secondary to CBD will be documented.
Full Information
NCT ID
NCT04398446
First Posted
April 23, 2020
Last Updated
August 29, 2022
Sponsor
Main Line Health
Collaborators
Ananda Hemp, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04398446
Brief Title
Effect of Hemp-CBD on Patients With CIPN
Acronym
Coala-T-CBD
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
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 27, 2020 (Actual)
Primary Completion Date
November 30, 2022 (Anticipated)
Study Completion Date
April 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Main Line Health
Collaborators
Ananda Hemp, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chemotherapy-induced Peripheral Neuropathy, Colorectal Cancer Stage II, Colorectal Cancer Stage III, Breast Cancer, Ovarian Cancer, Uterine Cancer, Pancreatic Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
56 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Hemp-based CBD
Arm Type
Experimental
Arm Title
Placebo Oral Tablet
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Hemp-based CBD
Other Intervention Name(s)
Ananda Hemp CBD Spectrum Gelcaps
Intervention Description
3x Daily dosing for 12 weeks
Intervention Type
Other
Intervention Name(s)
Placebo oral tablet
Intervention Description
3x Daily dosing for 12 weeks
Primary Outcome Measure Information:
Title
Change in pressure/touch sensation during intervention and at follow-up
Description
At regular intervals, CIPN will be assessed by Semmes Weinstein Monofilament Examination using Touch-Test Sensory Evaluator Kit to determine pressure sensation.
Time Frame
Every two weeks for twelve weeks during intervention; One month follow-up
Title
Change in pain sensation during intervention and at follow-up
Description
At regular intervals, CIPN will be assessed by pinprick examination to determine pain sensation.
Time Frame
Every two weeks for twelve weeks during intervention; One month follow-up
Title
Change in vibration sensation during intervention and at follow-up
Description
At regular intervals, CIPN will be assessed by 128Hz tuning fork vibration test to determine vibration sensation.
Time Frame
Every two weeks for twelve weeks during intervention; One month follow-up
Title
Change in quality of life
Description
Quality of life will be measured by European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire, a validated 30-item questionnaire to assess treatment impact on quality of life in cancer patients on 4-point scales, where 4 is most severe.
Time Frame
Every two weeks for twelve weeks during intervention; One month follow-up
Title
Change in CIPN symptom severity
Description
CIPN symptoms will be measured by EORTC QLQ-CIPN20 Questionnaire, validated 20-item questionnaire to assess symptom severity of chemotherapy-induced peripheral neuropathy on 4-point scales, where 4 is most severe.
Time Frame
Every two weeks for twelve weeks during intervention; One month follow-up
Title
Change in pain severity
Description
Pain severity will be measured by Brief Pain Inventory (BPI) Short Form, validated 9-item questionnaire to assess the severity of pain and the impact of pain on daily functions on 10-point scales, where 10 is most severe.
Time Frame
Every two weeks for twelve weeks during intervention; One month follow-up
Title
Change in sleep quality
Description
Sleep quality will be measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Questionnaire, validated 8-item questionnaire to assess sleep quality on 5-point scales, where 5 is the most severe.
Time Frame
Every two weeks for twelve weeks during intervention; One month follow-up
Secondary Outcome Measure Information:
Title
Receptivity and accrual rate to clinical studies involving cannabis-based substances.
Description
Receptivity to clinical trials as well as to the use of CBD will be assessed using a questionnaire that will be distributed to all patients at the first encounter. Responses to this questionnaire will provide information regarding in the use of CBD was influencing factor for those who chose to participate or deferring factor for those who decline participation.
Time Frame
1 Day
Title
Adherence to CBD Products
Description
Adherence will be assessed with a Dosing Diary.
Time Frame
Daily, 12 weeks
Title
Rate of side effects using medical-grade CBD concentrates
Description
Side effects will be assessed at each encounter clinical evaluation by patient report in a Dosing Diary. All side effects thought to be secondary to CBD will be documented.
Time Frame
Daily, 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marisa Weiss, MD
Organizational Affiliation
Main Line Health System
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lankenau Medical Center
City
Wynnewood
State/Province
Pennsylvania
ZIP/Postal Code
19096
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
29388063
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.
Results Reference
background
PubMed Identifier
23788859
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.
Results Reference
background
PubMed Identifier
23788891
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.
Results Reference
background
PubMed Identifier
18360567
Citation
Saif MW, Reardon J. Management of oxaliplatin-induced peripheral neuropathy. Ther Clin Risk Manag. 2005 Dec;1(4):249-58.
Results Reference
background
PubMed Identifier
17405895
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.
Results Reference
background
PubMed Identifier
21737705
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.
Results Reference
background
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Effect of Hemp-CBD on Patients With CIPN
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