The Effect of Cannabis in Pancreatic Cancer

ID: NCT03245658
Status: Not yet recruiting
Phase: Phase 2
Start Date: October 06, 2017
First Submitted: March 21, 2017
Last Updated: August 09, 2017
Results: N/A
Sponsors & Collaborators: Jens Rikardt Andersen, Augustinus Fonden, Københavns Universitet, Familien Hede Nielsens Fond
Location: Denmark
Conditions: Neoplasms Pancreatic, Cachexia; Cancer, Cannabis, Appetite Loss, Palliative Medicine, Morbidity, Mortality
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Study Description

Brief Summary

The prevalence of malnutrition is overwhelming in pancreatic cancer patients, >80% experience a weight loss >10% of their habitual weight, which may develop into cancer cachexia. Cachexia may cause decreased quality of life, increased mortality and morbidity e.g. poorer response to antitumor treatment, longer length of stay, higher complications rate and shorter life expectancy. There is currently no effective treatment of cancer cachexia, but clinical research in medical cannabis show promising results. The cannabinoids THC and CBD show the highest pharmacological effect, but cannabis consists of >70 cannabinoids. THC and CBD exert their effect on the endocannabinoid system which modulate physiological systems such as pain, inflammation, appetite and energy balance. Thus, this potential orexigenic effect from THC and CBD may improve the nutritional state in patients with pancreatic cancer. Taking the above scientific rationale and the lack of evidence into account, the relevance of this clinical trial appears high.

This clinical trial is an eight-week crossover design examining the effects of the cannabinoids THC and CBD on energy- and protein intake and lean body mass as a measure of appetite, nausea and quality of life. A characterization of the metabolism is analysed through a metabolomics analysis.

Detailed Description

The aim is to investigate the effect of the cannabinoids THC (tetrahydrocannabinol) and CBD (cannabidiol) on energy- and protein intake and lean body mass in patients with pancreatic cancer. A metabolomics analysis is conducted to determine the simultaneous and quantitative intracellular metabolites when medical cannabis is administered in patients with pancreatic cancer.

The clinical trial is designed as a crossover intervention trial with a four week intervention period and a four week control period. The study subjects are instructed to administer individual titered doses of medical cannabis during the intervention period. Dietary history, height, weight, bio- impedance, VAS scales and quality of life measurements are conducted at baseline, every second week and at the end of the clinical trial. Six study subjects are invited to a semi-structured interview. Blood samples and urine samples are used for the metabolomics analysis thus a research biobank is established.

Study population: 32 study subjects diagnosed with pancreatic cancer in palliative care are included. Inclusions criteria: adult, weight loss > 5% of habitual weight. Able to understand and read Danish. Exclusion criteria: regular use of cannabis, psychiatric disorders e.g. Anorexia Nervosa, alcohol abuse, life expectancy

Descriptive statistics is used to characterize the study population. The statistical analysis is carried out in R-Project and all primary data are analyzed as intention-to-treat. P value 90% of patients with pancreatic cancer in the palliative phase experience reduced energy- and protein intake. The quantity of the reduction is, however, very poorly described and appear to depend on cancer progression.

The trial which is approved by the Research Ethics Committee is expected to commence May 2017 after approval by the Danish Medicines Agency and the Data Protection Agency. The clinical trial finish no later than February the 6th 2018. The specified time limit is due to the trial is also basis for a master's thesis in Clinical Nutrition at the Department of Nutrition, Exercise and Sports, University of Copenhagen. A PhD based on this master thesis will proceed afterwards. Taking into account the patients' usual control times and to minimize dropout, patient inclusion takes place ongoing, so that there is a control- and intervention period at the same time. Outcome measurements including anthropometry and dietary interviews are carried out at baseline, every two weeks and at the termination of each period. Quality of life measurements and VAS scales are filled out weekly in both periods. The semi-structured interview is carried out at the end of the clinical trial.

The results are going to be published, this applies to both positive, inconclusive and negative results. The clinical trial is registered in the two trial databases ClinicalTrials.gov and EudraCT (clinicaltrialsregister.eu). Scientific articles based on the findings are submitted to relevant journals such as The American Journal of Clinical Nutrition (2014 Impact Factor: 6.770). The results are furthermore used in a master`s thesis in Clinical Nutrition at the Department of Nutrition, Exercise and Sports, University of Copenhagen by Ninette Renee Jensen and Rikke Lundsgaard Nielsen. The results will be presented at congresses. reported in scientific articles, in the master"s thesis, in the information material, on the department's website, at the public master ́s thesis defense as well as at future congresses, or wherever desired. When the clinical trial is completed a report is sent to relevant authorities including the Research Ethics Committee and the Danish Medicines Agency within 90 days of completion.

Necessary permits from the Data Protection Agency, the Danish Medicines Agency and the Research Ethics Committee are obtained before the initiation of the clinical trial. The protocol is approved by the Research Ethics Committee. Side effects caused by medical cannabis varies in the literature, thus an individual titration period is implemented. No fatal cases have been reported with the use of medical cannabis in human clinical trials. Potential beneficial effects are expected when the study subjects are being treated with medical cannabis, since a gain in appetite and quality of life is expected through a modulation in the endocannabinoid system. Patients are informed that the drug is discontinued after the intervention period. The two master's thesis students review patient charts weekly to evaluate potential side effects to the drug. The clinical trial is terminated immediately in case of serious side effects. Relevant information material is handed out to the study subjects.

Upon loss of muscle mass and function as seen in cancer cachexia, the administration of individually titrated doses of medical cannabis could hypothetically slow down the condition further, by affecting any negative protein - and energy balance through the endocannabinoid system. When relieving cancer cachexia and improving steady-state, we expect improved prognosis's for the included patients

The overall objective of the study is that it must be orientated towards clinical significance, so that it can be implemented in clinical practice, thus benefit patients with cancer. The short-term goal is that the patients in this trial experience positive effects in terms of increased appetite and quality of life. Positive effects may contribute to increased research into this area thus resulting in improved evidence. In the longer term, the aim is that the results from this study may contribute to a treatment protocol on malnutrition recommending the use of medical cannabis based on high scientific evidence, so a larger group of patients with cancer may benefit. The results from the study may be used for recommendations on doses, side effects and likely beneficial effects when administer medical cannabis. The metabolomics analysis can contribute to a improved understanding of the cancer cachexia pathophysiology and management in a more experimental matter.
Condition or disease Intervention/treatment Phase

Appetite Loss

Cachexia; Cancer

Cannabis

Morbidity

Mortality

Neoplasms Pancreatic

Palliative Medicine

Drug: THC and CBD Mixture
Other Names
Medical cannabis oral drops
Phase 2

Tracking Information

First Submitted DateMarch 21, 2017
Last Update Posted DateAugust 09, 2017
Anticipated Start DateOctober 06, 2017
Anticipated Completion DateOctober 06, 2018
Anticipated Primary Completion DateMay 06, 2018
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Energy and protein intake [Time Frame: The outcome measure will be assessed at day 0 and at week 4]

    Dietary history (% of estimated needs - NRS 2002)

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Lean body mass [Time Frame: The outcome measure will be assessed at day 0 and at week 4]

    Bioimpedance (% of body weight, kg)

  • Appetite 1 [Time Frame: The outcome measure will be assessed at day 0 and at week 4]

    VAS (cm on 10 cm scale)

  • Appetite 2 [Time Frame: The outcome measure will be assessed at day 0 and at week 4]

    Dietary history (VAS (cm on 10 cm scale))

  • Appetite 3 [Time Frame: The outcome measure will be assessed at day 0 and at week 4]

    EORTC QLQ-C30 (score, standard for the Quality of Life entity)

  • Appetite 4 [Time Frame: The outcome measure will be assessed at day 0 and at week 4]

    EORTC QLQ-PAN26 (score, standard for the Quality of Life entity)

  • Quality of life 1 [Time Frame: The outcome measure will be assessed at day 0 and at week 4]

    EORTC QLQ-C30 (score, standard for the Quality of Life entity)

  • Quality of life 2 [Time Frame: The outcome measure will be assessed at day 0 and at week 4]

    EORTC QLQ-PAN26 (score, standard for the Quality of Life entity)

  • Quality of life 3 [Time Frame: The outcome measure will be assessed at day 0 and at week 4]

    VAS (VAS (cm on 10 cm scale))

  • Pain 1 [Time Frame: The outcome measure will be assessed at day 0 and at week 4]

    EORTC QLQ-C30 (score, standard for the Quality of Life entity)

  • Pain 2 [Time Frame: The outcome measure will be assessed at day 0 and at week 4]

    EORTC QLQ-PAN26 (score, standard for the Quality of Life entity)

  • Pain 3 [Time Frame: The outcome measure will be assessed at day 0 and at week 4]

    VAS (VAS (cm on 10 cm scale))

  • Mortality (8 weeks) [Time Frame: 8 weeks]

    Patient records, national register

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleThe Effect of Cannabis in Pancreatic Cancer
Official TitleThe Effect of Medical Cannabis Inpatients With Palliative Pancreatic Cancer
Brief Summary

The prevalence of malnutrition is overwhelming in pancreatic cancer patients, >80% experience a weight loss >10% of their habitual weight, which may develop into cancer cachexia. Cachexia may cause decreased quality of life, increased mortality and morbidity e.g. poorer response to antitumor treatment, longer length of stay, higher complications rate and shorter life expectancy. There is currently no effective treatment of cancer cachexia, but clinical research in medical cannabis show promising results. The cannabinoids THC and CBD show the highest pharmacological effect, but cannabis consists of >70 cannabinoids. THC and CBD exert their effect on the endocannabinoid system which modulate physiological systems such as pain, inflammation, appetite and energy balance. Thus, this potential orexigenic effect from THC and CBD may improve the nutritional state in patients with pancreatic cancer. Taking the above scientific rationale and the lack of evidence into account, the relevance of this clinical trial appears high.

This clinical trial is an eight-week crossover design examining the effects of the cannabinoids THC and CBD on energy- and protein intake and lean body mass as a measure of appetite, nausea and quality of life. A characterization of the metabolism is analysed through a metabolomics analysis.

Detailed Description

The aim is to investigate the effect of the cannabinoids THC (tetrahydrocannabinol) and CBD (cannabidiol) on energy- and protein intake and lean body mass in patients with pancreatic cancer. A metabolomics analysis is conducted to determine the simultaneous and quantitative intracellular metabolites when medical cannabis is administered in patients with pancreatic cancer.

The clinical trial is designed as a crossover intervention trial with a four week intervention period and a four week control period. The study subjects are instructed to administer individual titered doses of medical cannabis during the intervention period. Dietary history, height, weight, bio- impedance, VAS scales and quality of life measurements are conducted at baseline, every second week and at the end of the clinical trial. Six study subjects are invited to a semi-structured interview. Blood samples and urine samples are used for the metabolomics analysis thus a research biobank is established.

Study population: 32 study subjects diagnosed with pancreatic cancer in palliative care are included. Inclusions criteria: adult, weight loss > 5% of habitual weight. Able to understand and read Danish. Exclusion criteria: regular use of cannabis, psychiatric disorders e.g. Anorexia Nervosa, alcohol abuse, life expectancy

Descriptive statistics is used to characterize the study population. The statistical analysis is carried out in R-Project and all primary data are analyzed as intention-to-treat. P value 90% of patients with pancreatic cancer in the palliative phase experience reduced energy- and protein intake. The quantity of the reduction is, however, very poorly described and appear to depend on cancer progression.

The trial which is approved by the Research Ethics Committee is expected to commence May 2017 after approval by the Danish Medicines Agency and the Data Protection Agency. The clinical trial finish no later than February the 6th 2018. The specified time limit is due to the trial is also basis for a master's thesis in Clinical Nutrition at the Department of Nutrition, Exercise and Sports, University of Copenhagen. A PhD based on this master thesis will proceed afterwards. Taking into account the patients' usual control times and to minimize dropout, patient inclusion takes place ongoing, so that there is a control- and intervention period at the same time. Outcome measurements including anthropometry and dietary interviews are carried out at baseline, every two weeks and at the termination of each period. Quality of life measurements and VAS scales are filled out weekly in both periods. The semi-structured interview is carried out at the end of the clinical trial.

The results are going to be published, this applies to both positive, inconclusive and negative results. The clinical trial is registered in the two trial databases ClinicalTrials.gov and EudraCT (clinicaltrialsregister.eu). Scientific articles based on the findings are submitted to relevant journals such as The American Journal of Clinical Nutrition (2014 Impact Factor: 6.770). The results are furthermore used in a master`s thesis in Clinical Nutrition at the Department of Nutrition, Exercise and Sports, University of Copenhagen by Ninette Renee Jensen and Rikke Lundsgaard Nielsen. The results will be presented at congresses. reported in scientific articles, in the master"s thesis, in the information material, on the department's website, at the public master ́s thesis defense as well as at future congresses, or wherever desired. When the clinical trial is completed a report is sent to relevant authorities including the Research Ethics Committee and the Danish Medicines Agency within 90 days of completion.

Necessary permits from the Data Protection Agency, the Danish Medicines Agency and the Research Ethics Committee are obtained before the initiation of the clinical trial. The protocol is approved by the Research Ethics Committee. Side effects caused by medical cannabis varies in the literature, thus an individual titration period is implemented. No fatal cases have been reported with the use of medical cannabis in human clinical trials. Potential beneficial effects are expected when the study subjects are being treated with medical cannabis, since a gain in appetite and quality of life is expected through a modulation in the endocannabinoid system. Patients are informed that the drug is discontinued after the intervention period. The two master's thesis students review patient charts weekly to evaluate potential side effects to the drug. The clinical trial is terminated immediately in case of serious side effects. Relevant information material is handed out to the study subjects.

Upon loss of muscle mass and function as seen in cancer cachexia, the administration of individually titrated doses of medical cannabis could hypothetically slow down the condition further, by affecting any negative protein - and energy balance through the endocannabinoid system. When relieving cancer cachexia and improving steady-state, we expect improved prognosis's for the included patients

The overall objective of the study is that it must be orientated towards clinical significance, so that it can be implemented in clinical practice, thus benefit patients with cancer. The short-term goal is that the patients in this trial experience positive effects in terms of increased appetite and quality of life. Positive effects may contribute to increased research into this area thus resulting in improved evidence. In the longer term, the aim is that the results from this study may contribute to a treatment protocol on malnutrition recommending the use of medical cannabis based on high scientific evidence, so a larger group of patients with cancer may benefit. The results from the study may be used for recommendations on doses, side effects and likely beneficial effects when administer medical cannabis. The metabolomics analysis can contribute to a improved understanding of the cancer cachexia pathophysiology and management in a more experimental matter.

Study TypeInterventional
Study PhasePhase 2
Estimated Enrollment
32
Allocation
Randomized
Interventional Model
Crossover Assignment
Masking
None
Primary Purpose
Treatment
Conditions
Appetite Loss
Cachexia; Cancer
Cannabis
Morbidity
Mortality
Neoplasms Pancreatic
Palliative Medicine
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: THC and CBD Mixture

Individually titrated doses on daily basis

Other Names
Medical cannabis oral drops
Study Groups/Cohorts
THC and CBD Mixture
32 patients with palliative pancreatic cancer, intervention with oral drops of THC, 25mg/ml and CBD 50mg/ml, daily administered for 4 weeks

Control
32 patients with palliative pancreatic cancer, no experimental treatment,

Study Arms
Experimental THC and CBD Mixture
32 patients with palliative pancreatic cancer, intervention with oral drops of THC, 25mg/ml and CBD 50mg/ml, daily administered for 4 weeks
Drug : THC and CBD Mixture
Individually titrated doses on daily basis

Arm Intervention/Treatment
Experimental THC and CBD Mixture
32 patients with palliative pancreatic cancer, intervention with oral drops of THC, 25mg/ml and CBD 50mg/ml, daily administered for 4 weeks
Drug : THC and CBD Mixture

Recruitment Information

Recruitment Status:Not yet recruiting
Enrollment32
Completion DateOctober 06, 2018
Eligibility Criteria: Inclusion Criteria:
- Adult, palliative pancreatic cancer diagnosis, weight loss > 5%, understand and read Danish.

Exclusion Criteria:
- Regular use of cannabis, psychiatric disorders, alcohol abuse, life expectancy < 6 months
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Denmark

Administrative Information

NCT Number:NCT03245658
Other Study ID Numbers
H-17000277
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible PartyJens Rikardt Andersen, University of Copenhagen
Study Sponsor
Jens Rikardt Andersen
Collaborators
Augustinus Fonden
Københavns Universitet
Familien Hede Nielsens Fond
Investigators
Principal Investigator
Jens Rikardt Andersen, MD, MPA
University of Copenhagen