Ghrelin in Cystic Fibrosis (ghrelin)

The Effect of Ghrelin on Appetite and Immune Function in Patients With Cystic Fibrosis

Background to ghrelin Ghrelin is a naturally occurring hormone found in the blood which stimulates appetite. In healthy individuals, levels of ghrelin are high before a meal and falls afterwards. Previous studies have shown that giving ghrelin (by injection) to thin patients with renal failure and cancer increases their food intake. Furthermore, addition of ghrelin may also reduce inflammation within the body. Cystic Fibrosis (CF) is a genetic disease which frequently results in recurrent lung infections (leading to progressive inflammatory lung damage) and low body weight. Low body weight in CF is associated with increased lung infections, rapidly worsening lung function and a shortened life expectancy.

The researchers postulate that administration of extra ghrelin to CF patients with low body weight may increase food intake and reduce lung inflammation. If successful, this study might identify ghrelin as a potential therapy for CF patients to improve nutrition, decrease lung inflammation and thereby improve survival.

Study Overview

• Status: Unknown
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Biological: ghrelin

Detailed Description

The purpose of this study is to investigate the role of a naturally occuring hormone called ghrelin on appetite, energy expenditure and immune function in patients with cystic fibrosis.

Theoretical framework:

Despite advances in the molecular understanding of the disease, life-expectancy in Cystic Fibrosis (CF) remains severely limited. Reduced body-weight is associated with increased inflammatory lung damage and is a major predictor of mortality in CF patients. Malnutrition is highly prevalent in the CF population and results from both poor food intake and excessive energy expenditure. A therapy which improves nutrition may therefore have a significant effect on the prognosis of this disease. Ghrelin is the only physiological circulating factor that is known to increase food intake. Administration of acylated ghrelin to humans increases both hunger and food intake and has been found to increase appetite in chronic disease states associated with anorexia and weight loss (such as cancer and chronic renal disease). From multiple animal and in vitro human studies, ghrelin also appears to have anti-inflammatory properties which would potentially benefit CF patients in whom a chronic inflammatory state promotes lung destruction, malnutrition and increases mortality. Ghrelin replacement may therefore improve nutrition and decrease the inflammatory burden in CF patients, leading to an improvement in life-expectancy. If ghrelin is identified as having an important pathophysiological role in CF it may lead to a future study of its efficacy as a therapeutic agent.

Design Methodology: The study has three sections:

1. a cross sectional study of the levels of blood metabolic signals in participants with cystic fibrosis and healthy controls.
2. a laboratory study of the effect of ghrelin on immune cells extracted from the blood of participants with cystic fibrosis and healthy controls
3. a cross-over interventional study of repeated ghrelin administration in malnourished cystic fibrosis patients

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB23 3RE
      • Recruiting
      • Papworth Hospital NHS Foundation Trust
      • Contact: Andres R Floto, BM BSc, PhD; Phone Number: 01480 830541; Email: andres.floto@papworth.nhs.uk
      • Contact: Jane D Elliott, MPhil; Phone Number: 01480 364495
      • Principal Investigator: Andres Floto, MB BChir, PhD, FRCP
      • Sub-Investigator: Katie J Wynne, MB BChir, PhD, FRCP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Cystic fibrosis
• BMI </=19 kg/m2

Exclusion Criteria:

• Needle phobia
• Pulmonary infection requiring intravenous antibiotics in the past 2 weeks-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: saline injections	Biological: ghrelin; subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Appetite	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
weight	4 weeks

Collaborators and Investigators

• Sponsor: Papworth Hospital NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Anticipated): February 1, 2011
• Study Completion (Anticipated): April 1, 2011

Study Registration Dates

• First Submitted: September 30, 2008
• First Submitted That Met QC Criteria: September 30, 2008
• First Posted (Estimate): October 1, 2008

Study Record Updates

• Last Update Posted (Estimate): July 27, 2010
• Last Update Submitted That Met QC Criteria: July 26, 2010
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Keywords: Cystic fibrosis; Weight; Appetite; Ghrelin; Cystic fibrosis with low BMI
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: P01276