Role of Myostatin, Activin A and Follistatin Cachexia of ENT Cancers (MYOCACH)

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.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer; Cachexia; Squamous Cell Carcinoma
• Intervention / Treatment: Procedure: Tumor removal

Detailed 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.

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• France
  • Auvergne
    • Clermont-Ferrand, Auvergne, France, 63003
      • CHU Clermont-Ferrand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

55 patients were included in the study : 32 in the cancer group (only squamous cell carcinoma) and 23 in the control group.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Squamous cell carcinoma; 55 patients were included in the study : 32 in the cancer group (only squamous cell carcinoma) and 23 in the control group.	Procedure: Tumor removal; Surgery
Control group; 55 patients were included in the study : 32 in the cancer group (only squamous cell carcinoma) and 23 in the control group.	Procedure: Tumor removal; Surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 2, 2015
• Primary Completion (ACTUAL): February 1, 2016
• Study Completion (ACTUAL): May 1, 2017

Study Registration Dates

• First Submitted: May 5, 2017
• First Submitted That Met QC Criteria: May 19, 2017
• First Posted (ACTUAL): May 22, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 22, 2017
• Last Update Submitted That Met QC Criteria: May 19, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Follistatin; Cachexia; Squamous cell carcinoma; Activin A; Myostatin
• Additional Relevant MeSH Terms: Metabolic Diseases; Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Nutrition Disorders; Body Weight; Body Weight Changes; Neoplasms, Squamous Cell; Emaciation; Weight Loss; Carcinoma, Squamous Cell; Wasting Syndrome; Cachexia
• Other Study ID Numbers: CHU-326; 2015-A00833-46 (OTHER: 2015-A00833-46)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No