Nabilone Effect on the Attenuation of Anorexia, Nutritional Status and Quality of Life in Lung Cancer Patients

August 29, 2016 updated by: Oscar Gerardo Arrieta Rodríguez MD, Instituto Nacional de Cancerologia de Mexico

Nabilone Effect on the Attenuation of Anorexia, Nutritional Status and Quality of Life in Patients With Anorexia Associated With Advanced Lung Cancer: Randomized Double Blind Clinical Trial

Anorexia is common symptom in cancer patients and is associated with increased morbidity and mortality. However timely detection with objective tools is necessary to establish the diagnosis of anorexia and to assess the magnitude of change over time. The anorexia pathophysiology is not clearly understood and treatment options are limited. Anecdotal historical benefits of smoking marijuana on nausea, pain and anorexia led to studies with marijuana and synthetic cannabinoids from Δ-9-tetrahydrocannabinol, the main active agent in marijuana. The endogenous cannabinoid system with its receptors CB1 and CB2 regulate appetite in four functional levels: (1) limbic system (hedonistic quality), (2) hypothalamus (appetite stimulant), (3) intestinal, and (4) tissue adipose.

Nabilone, a synthetic analogue of THC approved in Mexico for nausea and vomiting induced by chemotherapy is also used in palliative care units for clinical improvement in increased appetite patients in terminal stages, however, there are no clinical trials demonstrating this benefit.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Background: Lung cancer is the leading cause of cancer death in Mexico and the world. Malnutrition is often associated with this type of cancer appearing in about 40-50% of patients the diagnosis made, affecting the quality of life and prognosis, as well as increased toxicity to cancer treatment. Cancer anorexia is characterized by loss of appetite and is the main cause of reduced food consumption in lung cancer patients. Anorexia occurs in up to 25% of cases. Unfortunately, current therapies available to treat anorexia and / or cachexia associated with cancer provide only partial results, mainly because the intervention is delayed and the development of an early and effective intervention is still looking.

In most patients, malnutrition is associated with a hyporexia secondary to the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF), leading to an increase in metabolism and appetite loss. Nabilone is a synthetic cannabinoid derivative that is widely used in oncology for its antiemetic and adjuvant effect of pain. Although widely used for the treatment of anorexia in palliative care, no randomized clinical trials demonstrating an effect on cancer-associated anorexia, however, in animal models, stimulation of cannabinoid receptors, mainly through CB1 receptor can modulate hypothalamic circuits in the brain stem, which in turn regulate food intake and satiety. Moreover cannabinoids are able to block the effects of TNF in the nervous system, which is associated with appetite changes in cancer patients. Additionally, agonists of cannabinoid receptors attenuated weight loss in murine models of anorexia.

Additionally, to diagnosis anorexia The Anorexia-Cachexia scale (A/CS-12) from The Functional Assessment of Anorexia-Cachexia therapy (FAACT) questionnaire relates differences in symptoms and severity, assigning a value of 0-4 for each of 12 items. A 2010 consensus of special interest group of CACS from ESPEN (The European Society for Clinical Nutrition and Metabolism) in order to unify criteria, proposed that a score ≤24 of the A/CS-12 would be enough to establish a diagnosis of anorexia.

The administration of Nabilone in patients with anorexia associated with Non-Small Cell Lung Cancer (NSCLC) is expected to increase appetite, nutritional status and quality of life.

Methods: randomized double-blind clinical trial assessing Nabilone effect in non-small cell lung cancer (NSCLC) patients with unresectable stage III/IV NSCLC, ECOG performance status (ECOG PS) 1-2 and anorexia (main criteria: score of Anorexia Cachexia scale (AC/S-12) from Functional Assessment of Anorexia Cachexia Therapy ≤24). Patients are randomized to Nabilone at 0.5mg to 1mg, or placebo, given daily orally for 8 weeks. Changes are evaluated from baseline to week 2, 4, and 8.

Time Assessment Dose T0 Baseline 0.5mg T1 2 weeks 1 mg T2 4 weeks 1 mg T3 8 weeks 1 mg

Sample size:

To determine the sample size is considered the effect of cannabinoid (dronabinol, 2.5 mg / 22 days) in appetite in cancer patients by a difference in proportions of 34% more than placebo, requiring 32 patients per group plus 20% of loss gives us a total of 39 patients per group, with a power of 90% and an α of 0.05

Study Type

Interventional

Enrollment (Anticipated)

78

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
      • Mexico City, Mexico, 14080
        • Recruiting
        • Instituto Nacional de Cancerologia
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Non-small cell lung cancer (NSCLC) patients with unresectable stage IIIB/IV
  • ECOG performance status ≤2
  • Life expectancy of > 4 months at time of screening
  • If woman of childbearing potential or a fertile man, he/she must agree to use an effective form of contraception during the study and for 30 days following the last dose of study drug (an effective form of contraception is abstinence, a hormonal contraceptive, or a double-barrier method)
  • Must be willing and able to give signed informed consent and, in the opinion of the Investigator, to comply with the protocol tests and procedures

Exclusion Criteria:

  • Known allergy to some derivative of marijuana, there is a dependency or who have previously been treated with cannabinoids.
  • Consumption of dietary supplements at baseline.
  • Currently taking prescription medications intended to increase appetite or treat weight loss; these include, but are not limited to, testosterone, androgenic compounds, megestrol acetate, methylphenidate, and Anamorelin.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Nabilone
Patients start receiving a dose of 0.5 mg daily oral nabilone the first 2 weeks and then 1 mg to complete 8 weeks.
Drug: Nabilone
Patients going to take 0.5 mg capsules of nabilone (CESAMET) the first 2 weeks and then increased to 1 mg to complete 8 weeks.
Other Names:
  • cesamet
PLACEBO_COMPARATOR: placebo
Patients start receiving a dose of 0.5 mg daily oral placebo the first 2 weeks and then 1 mg to complete 8 weeks.
Drug: Placebo
Patients going to take capsules of placebo until complete 8 weeks.
Other Names:
  • placebo nabilona

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
anorexia
Time Frame: from the start of consumption until 8 weeks.
Lack of desire to eat food. Will be obtained through a questionnaire Anorexia / Cachexia scale from Functional Assessment of Anorexia Cachexia Therapy (FAACT) (score ≤24 diagnosis of anorexia)
from the start of consumption until 8 weeks.
percentage weight loss
Time Frame: from the start of consumption until 8 weeks.
percentage weight loss in the last month
from the start of consumption until 8 weeks.
Body Mass Index
Time Frame: from the start of consumption until 8 weeks.
It is an index of a person's weight in relation to height
from the start of consumption until 8 weeks.
Subjective Global Assessment
Time Frame: from the start of consumption until 8 weeks.
convenient, fast and cheaper method used to make a nutritional assessment, consisting of 3 parts: anamnesis, physical examination and qualification.
from the start of consumption until 8 weeks.
energy consumption
Time Frame: from the start of consumption until 8 weeks.
Total calories consumed on average per day for a subject
from the start of consumption until 8 weeks.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
protein consumption
Time Frame: from the start of consumption until 8 weeks.
Total protein grams consumed on average per day for a subject
from the start of consumption until 8 weeks.
lipids consumption
Time Frame: from the start of consumption until 8 weeks.
Total lipids grams consumed on average per day for a subject
from the start of consumption until 8 weeks.
carbohydrate consumption
Time Frame: from the start of consumption until 8 weeks.
Total carbohydrate grams consumed on average per day for a subject
from the start of consumption until 8 weeks.
nausea
Time Frame: from the start of consumption until 8 weeks.
adverse effect from Common terminology criteria for adverse event
from the start of consumption until 8 weeks.
vomiting
Time Frame: from the start of consumption until 8 weeks.
adverse effect from Common terminology criteria for adverse event
from the start of consumption until 8 weeks.
constipation
Time Frame: from the start of consumption until 8 weeks.
adverse effect from Common terminology criteria for adverse event
from the start of consumption until 8 weeks.
Diarrhea
Time Frame: from the start of consumption until 8 weeks.
adverse effect from Common terminology criteria for adverse event
from the start of consumption until 8 weeks.
Dysgeusia
Time Frame: from the start of consumption until 8 weeks.
adverse effect from Common terminology criteria for adverse event
from the start of consumption until 8 weeks.
Global Status of Quality of Life
Time Frame: from the start of consumption until 8 weeks.
The Global status of Quality of Life evaluation is evaluated using the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaires specific for cancer with the items 29 and 30.
from the start of consumption until 8 weeks.
Physical functioning
Time Frame: from the start of consumption until 8 weeks.
The Physical functioning evaluation is evaluated from the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaires specific for cancer
from the start of consumption until 8 weeks.
Role Functioning
Time Frame: from the start of consumption until 8 weeks.
The Role functioning evaluation is evaluated from the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaires specific for cancer
from the start of consumption until 8 weeks.
Emotional Functioning
Time Frame: from the start of consumption until 8 weeks.
The Emotional Functioning evaluation is evaluated from the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaires specific for cancer
from the start of consumption until 8 weeks.
Social Functioning
Time Frame: from the start of consumption until 8 weeks.
The Social Functioning evaluation is evaluated from the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaires specific for cancer
from the start of consumption until 8 weeks.
Nausea/Vomiting
Time Frame: from the start of consumption until 8 weeks.
The Nausea/Vomiting evaluation is evaluated from the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaires specific for cancer
from the start of consumption until 8 weeks.
Fatigue
Time Frame: from the start of consumption until 8 weeks.
The Fatigue evaluation is evaluated from the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaires specific for cancer
from the start of consumption until 8 weeks.
appetite loss
Time Frame: from the start of consumption until 8 weeks.
The appetite loss evaluation is evaluated from the validated Mexican-Spanish version of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaires specific for cancer
from the start of consumption until 8 weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Nacional de Cancerologia de Mexico

Investigators

  • Principal Investigator: Oscar Arrieta, MD M Sc, Instituto Nacional de Cancerologia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2014

Primary Completion (ANTICIPATED)

July 1, 2017

Study Completion (ANTICIPATED)

July 1, 2017

Study Registration Dates

First Submitted

May 22, 2016

First Submitted That Met QC Criteria

June 15, 2016

First Posted (ESTIMATE)

June 16, 2016

Study Record Updates

Last Update Posted (ESTIMATE)

August 31, 2016

Last Update Submitted That Met QC Criteria

August 29, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NABILONA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

publishing the results

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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