The Effect of Cannabis in Pancreatic Cancer
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| 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
Individually titrated doses on daily basis
Other Names:
|
| No Intervention: Control 32 patients with palliative pancreatic cancer, no experimental treatment, |
Outcome Measures
Primary Outcome Measures
- Energy and protein intake [The outcome measure will be assessed at day 0 and at week 4]
Dietary history (% of estimated needs - NRS 2002)
Secondary Outcome Measures
- Lean body mass [The outcome measure will be assessed at day 0 and at week 4]
Bioimpedance (% of body weight, kg)
- Appetite 1 [The outcome measure will be assessed at day 0 and at week 4]
VAS (cm on 10 cm scale)
- Appetite 2 [The outcome measure will be assessed at day 0 and at week 4]
Dietary history (VAS (cm on 10 cm scale))
- Appetite 3 [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 [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 [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 [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 [The outcome measure will be assessed at day 0 and at week 4]
VAS (VAS (cm on 10 cm scale))
- Pain 1 [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 [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 [The outcome measure will be assessed at day 0 and at week 4]
VAS (VAS (cm on 10 cm scale))
- Mortality (8 weeks) [8 weeks]
Patient records, national register
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of clinical oncology, Næstved-Roskilde Hospital | Naestved | Denmark | 4700 |
Sponsors and Collaborators
- Jens Rikardt Andersen
- Augustinus Fonden
- Københavns Universitet
- Familien Hede Nielsens Fond
Investigators
- Principal Investigator: Jens Rikardt Andersen, MD, MPA, University of Copenhagen
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- H-17000277