Cancer Anorexia and the Central Nervous System

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Alessandro Laviano, University of Roma La Sapienza
ClinicalTrials.gov Identifier:
NCT01564693
First received: March 14, 2012
Last updated: July 28, 2015
Last verified: July 2015
  Purpose

The pathogenesis of cancer anorexia is complex and multifactorial. However, a number of consistent and robust evidence point to a prominent role for the central nervous system. In particular, the hyperactivation of the immune system, due to tumour growth, causes a systemic inflammatory response primarily mediated by pro-inflammatory cytokines. At the central level, inflammatory response profoundly alters the activity of the hypothalamic nuclei, which are involved in the regulation of energy homeostasis. In particular, pro-inflammatory cytokines inhibit prophagic neurons activity, while enhance the activation of the anorexigenic neurons. Although supported by compelling experimental evidence, it should be acknowledged that this pathogenic hypothesis has not been confirmed yet by human studies.

Aim of the present study is to determine the specific pattern(s) of the brain activation after assumption of a standard meal in both anorexic and non-anorexic cancer patients to reveal potential differences, which will be correlated with the levels of concurrently measured circulating pro-inflammatory cytokines. The results obtained would help in assessing the role of the central nervous system and, in particular of the hypothalamus, in the pathogenesis of cancer anorexia.


Condition
Cancer Cachexia

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Neuroimaging of Hypothalamic Activity During Cancer Anorexia

Resource links provided by NLM:


Further study details as provided by University of Roma La Sapienza:

Primary Outcome Measures:
  • ACTIVATION/NON ACTIVATION OF SPECIFIC BRAIN AREAS, EVALUATED BY FUNCTIONAL MAGNETIC RESONANCE [ Time Frame: TIME 0 (BASELINE) ] [ Designated as safety issue: No ]
    We observed different BOLD signal in the region of the hypothalamus between the 3 groups. The BOLD signal and the activation/no activation areas were statistically analyzed by a specific statistical method (i.e., parametric mapping).


Biospecimen Retention:   Samples Without DNA
serum

Enrollment: 15
Study Start Date: April 2010
Study Completion Date: April 2015
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
ANOREXIC CANCER PATIENTS
Nine lung cancer patients were diagnosed as anorexic based on the results obtained by the appetite assessment tools we used. These patients were studied by fMRI regarding the hypothalamic activity.
NON-ANOREXIC CANCER PATIENTS
Four lung cancer patients were diagnosed as non-anorexic based on the results obtained by the appetite assessment tools we used. These patients were studied by fMRI regarding the hypothalamic activity.
CONTROL GROUP
Two healthy volunteers with normal appetite were studied by fMRI regarding the hypothalamic activity.

Detailed Description:

After approval of the study protocol by the Ethical Committee of our Institution (Azienda Policlinico Umberto I, Sapienza University, Rome, Italy), 9 anorexic cancer patients, 4 non-anorexic cancer patients and 2 healthy individuals will be studied. The sample size is based on studies of neuroimaging already published and available on international journals.

Patients with confirmed cancer diagnosis will be enrolled before the initiation of any anti-cancer treatments. The presence/absence of anorexia will be investigated using a specific questionnaire (Cangiano et al., 1990) and a visual analogue scale (VAS). After an overnight fasting, blood samples will be collected from cancer patients and control subjects and interleukin(IL)-1, IL-6 and Tumor Necrosis Factor-α (TNF-α) levels will be measured by a commercially available ELISA kit.

On the same day, hypothalamic activation pattern(s) will be evaluated in patients and in control subjects by fMRI. After basal evaluation, all the groups will receive a standard oral meal, i.e., a 200 mL hypercaloric oral nutritional supplement providing 300 Kcal, and then a second fMRI scan will be performed. Using a computerized software, the average value of the grey for the hypothalamus will be calculated, and normalized for the one obtained in the basal condition, to obtain the percentage (%) of activation (or inhibition) of the hypothalamus.

Data obtained will be statistically analyzed using the t-Student and Bonferroni tests.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Lung cancer patients with confirmed cancer diagnosis before the initiation of any anti-cancer treatments will be enrolled. Nine anorexic cancer patients, 4 non-anorexic cancer patients and 2 healthy individuals will be studied.
Criteria

Inclusion Criteria:

  • Lung cancer patients at diagnosis

Exclusion Criteria:

  • Patients treated with immunosuppressors, with concomitant wasting diseases (e.g. AIDS, trauma, end-stage renal disease)
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01564693

Locations
Italy
Department of Clinical Medicine, Sapienza University of Rome
Rome, Italy, 00185
Sponsors and Collaborators
University of Roma La Sapienza
Investigators
Principal Investigator: Alessandro Laviano, MD Sapienza University of Rome
  More Information

Responsible Party: Alessandro Laviano, MD, Associate Professor, University of Roma La Sapienza
ClinicalTrials.gov Identifier: NCT01564693     History of Changes
Other Study ID Numbers: FRFLAV 
Study First Received: March 14, 2012
Results First Received: April 23, 2015
Last Updated: July 28, 2015
Health Authority: Italy: Ethics Committee

Keywords provided by University of Roma La Sapienza:
anorexia
cancer
hypothalamus
inflammation

Additional relevant MeSH terms:
Anorexia
Cachexia
Signs and Symptoms, Digestive
Signs and Symptoms
Emaciation
Weight Loss
Body Weight Changes
Body Weight

ClinicalTrials.gov processed this record on August 28, 2016