Role of Myostatin, Activin A and Follistatin Cachexia of ENT Cancers

Head and Neck Cancer Clinical Trial

— MYOCACH  

Official title:

Role of Myostatin, Activin A and Follistatin Cachexia of ENT Cancers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03162042
• Other study ID #: CHU-326
• Secondary ID: 2015-A00833-46
• Status: Completed
• Phase: N/A
• First received: May 5, 2017
• Last updated: May 19, 2017
• Start date: November 2, 2015
• Est. completion date: May 2017

Study information

• Verified date: May 2017
• Source: University Hospital, Clermont-Ferrand
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The main objective of our study was to determine the modifications of blood myostatin and activin A concentrations associated with head and neck cancers. Secondary objectives consisted in studying their influence on the occurrence of cachexia, bringing the proof of a tumoral secretion of these factors, and then determining the effect of tumor removal.

Description:

Myostatin and activin A, two members of the superfamily TGF-β, have been shown to play a role on skeletal muscle mass regulation. In Humans, high plasma concentrations of activin A were observed in cancer patients, especially in cachectic subpopulations, suggesting their involvement in the development of cachexia.

55 patients were included in the study : 32 in the cancer group (only squamous cell carcinoma) and 23 in the control group. The patients underwent a complete nutritional assessment and multiple samples : blood before and 7 days after surgery, skeletal muscle biopsies, tumor biopsies. Plasma concentrations of myostatin, activin and follistatin were measured before and after tumor removal surgery. Concentrations of myostatin, activin and follistatin were also measured in an incubation medium of a tumor biopsy. Activin A and follistatin plasma concentrations were significantly increased in the cancer group (320 vs. 203 pg/ml ; p <0.001) (3593 vs 2148 pg/ml ; p <0.001), while myostatin plasma concentration was significantly decreased in this group (1542 vs. 2100 pg/ml ; p = 0.010). Surprisingly, data of the 7th postoperative day showed an increase in plasma activin A concentration (379 vs 320 pg /ml ; p <0.001) while concentrations of myostatin and follistatin were not modified. A high postoperative systemic inflammation is one hypothesis to explain these later results. Myostatin, activin A and follistatin proteins were systematically detected in the medium of tumor a 48 hour-incubation period, providing a strong proof of the tumor production of these factors by squamous cell carcinoma. The activin A/myostatin/follistatin is modified in the context of head and neck cancer. Activin A particularly seems to play a role in the occurrence of cachexia while follistatin could have a protective role for skeletal muscle mass. This system could aimed in therapeutic ways to reduce cachexia in a context of cancer in order to improve the quality of life and survival of patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: May 2017
• Est. primary completion date: February 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

For case group :

• head and neck cancer

• squamous cell carinoma only

• head and neck surgery chosen as treatment of cancer

• age 18-75

For control group :

• Neck surgery for non oncologic disease

• age 18-75

Exclusion Criteria:

• heart failure, respiratory failure (requiring a long-term oxygen therapy), chronic renal failure (MDRD clearance < 60 ml/min), moderate or severe chronic obstructive pulmonary disease and insulin-dependent diabeta for the two groups

• cachexia for control group

Related Conditions & MeSH terms

• Cachexia
• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Head and Neck Neoplasms
• Squamous Cell Carcinoma

Intervention

Procedure:
• Tumor removal
Surgery

Locations

Country	Name	City	State
France	CHU Clermont-Ferrand	Clermont-Ferrand	Auvergne

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Clermont-Ferrand

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure of plasma activin A (pg/ml)	determine the modifications of blood myostatin and activin A concentrations associated with head and neck cancers	at day 1
Primary	Measure of plasma follistation (pg/ml)	determine the modifications of blood myostatin and activin A concentrations associated with head and neck cancers	at day 1
Primary	Measure of plasma myostatin (pg/ml)	determine the modifications of blood myostatin and activin A concentrations associated with head and neck cancers	at day 1
Secondary	Influence on the occurrence of cachexia	Bringing the proof of a tumoral secretion of these factors, and then determining the effect of tumor removal.	at day 1