Cancer Anorexia and the Central Nervous System
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
|
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
Outcome Measures
Primary Outcome Measures
- ACTIVATION/NON ACTIVATION OF SPECIFIC BRAIN AREAS, EVALUATED BY FUNCTIONAL MAGNETIC RESONANCE [TIME 0 (BASELINE)]
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).
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- FRFLAV
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | ANOREXIC CANCER PATIENTS | NON-ANOREXIC CANCER PATIENTS | CONTROL GROUP |
|---|---|---|---|
| Arm/Group Description | We evaluated 9 patients with lung cancer who met the inclusion criteria and were enrolled in the study. According to the protocol, the presence of anorexia was assessed by appetite assessment tools. | According to the protocol, we evaluated 4 patients with lung cancer who met the inclusion criteria and were enrolled in the study. According to the protocol, the absence of anorexia was assessed by appetite assessment tools. | Two healthy volunteers were evaluated and included in the study as controls. Their appetite was normal, as assessed by appetite measurement tools. |
| Period Title: Overall Study | |||
| STARTED | 9 | 4 | 2 |
| COMPLETED | 9 | 4 | 2 |
| NOT COMPLETED | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | ANOREXIC CANCER PATIENTS | NON-ANOREXIC CANCER PATIENTS | CONTROL GROUP | Total |
|---|---|---|---|---|
| Arm/Group Description | Based on the anorexia instruments that we used, we considered these patients as anorexic. | Based on the anorexia instruments that we used, we considered these patients as non-anorexic | These were healthy subjects. 1 MD working at the Oncology Dept. , 1 family member of one of the patients enrolled. | Total of all reporting groups |
| Overall Participants | 9 | 4 | 2 | 15 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
2
22.2%
|
0
0%
|
1
50%
|
3
20%
|
| >=65 years |
7
77.8%
|
4
100%
|
1
50%
|
12
80%
|
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
71.1
(9.4)
|
76.25
(6.95)
|
65
(7.1)
|
71.66
(8.76)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
3
33.3%
|
3
75%
|
1
50%
|
7
46.7%
|
| Male |
6
66.7%
|
1
25%
|
1
50%
|
8
53.3%
|
| Region of Enrollment (participants) [Number] | ||||
| Italy |
9
100%
|
4
100%
|
2
100%
|
15
100%
|
Outcome Measures
| Title | ACTIVATION/NON ACTIVATION OF SPECIFIC BRAIN AREAS, EVALUATED BY FUNCTIONAL MAGNETIC RESONANCE |
|---|---|
| Description | 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). |
| Time Frame | TIME 0 (BASELINE) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | ANOREXIC CANCER PATIENTS | NON-ANOREXIC CANCER PATIENTS | CONTROL GROUP |
|---|---|---|---|
| Arm/Group Description | Patients revealed as anorexic were studied regarding BOLD signal activity by fMRI | Patients revealed as non-anorexic were studied regarding BOLD signal activity by fMRI | Healthy subjects were studied regarding BOLD signal activity by fMRI |
| Measure Participants | 9 | 4 | 2 |
| Mean (Standard Deviation) [BOLD] |
585.57
(55.69)
|
667.92
(33.18)
|
511.22
(79.43)
|
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | ANOREXIC CANCER PATIENTS | NON-ANOREXIC CANCER PATIENTS | CONTROL GROUP | |||
| Arm/Group Description | Nine patients were studied by fMRI before and after administration of a standard meal. The presence of serious adverse events (i.e., allergy, claustrophobia) were investigated. The presence of nausea and vomiting after the intake of the standard meal was also investigated. | Four patients were studied by fMRI before and after administration of a standard meal. The presence of serious adverse events (i.e., allergy, claustrophobia) were investigated. The presence of nausea and vomiting after the intake of the standard meal was also investigated. | Two volunteers were studied by fMRI before and after administration of a standard meal. The presence of serious adverse events (i.e., allergy, claustrophobia) were investigated. The presence of nausea and vomiting after the intake of the standard meal was also investigated. | |||
All Cause Mortality |
||||||
| ANOREXIC CANCER PATIENTS | NON-ANOREXIC CANCER PATIENTS | CONTROL GROUP | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| ANOREXIC CANCER PATIENTS | NON-ANOREXIC CANCER PATIENTS | CONTROL GROUP | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/4 (0%) | 0/2 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| ANOREXIC CANCER PATIENTS | NON-ANOREXIC CANCER PATIENTS | CONTROL GROUP | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/4 (0%) | 0/2 (0%) | |||
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | PROF. ALESSANDRO LAVIANO |
|---|---|
| Organization | SAPIENZA UNIVERSITY OF ROME |
| Phone | +390649973902 |
| alessandro.laviano@uniroma1.it |
- FRFLAV