The Altitude Inflammatory Bowel Disease Study

A Study on the Influence of Hypoxia on Healthy Volunteers and Patients With Inflammatory Bowel Disease (IBD): The Altitude IBD Study

This is a prospective, controlled and observational study. Participants underwent a 3-hour exposure to hypoxic conditions simulating an altitude of 4,000 meters above sea level (m.a.s.l.) in a hypobaric pressure chamber. Clinical parameters, as well as blood and stool samples and biopsies from the sigmoid colon (by sigmoidoscopy) are collected at subsequent time points. The investigators goal is to evaluate if a 3-hour stay at high altitude (4, 000 m) can alter disease activity and can modulate a pro inflammatory reaction.

Study Overview

• Status: Unknown
• Conditions: Inflammatory Bowel Disease
• Intervention / Treatment: Other: hypobaric pressure chamber; Other: Sigmoidoscopy

Detailed Description

To evaluate the potential influence of hypoxia on the course of IBD on a biomolecular level, and to test the effects of hypoxia under standardized conditions, the investigators initiated a prospective and controlled investigation in healthy controls and IBD patients in stable remission. the investigators primary aim is to show that a 3-hour stay at high altitude can alter disease activity of IBD. Ten healthy volunteers, 11 Crohn's disease (CD) patients and 9 ulcerative colitis (UC) patients underwent a 3-hour exposure to hypoxic conditions simulating an altitude of 4,000 m.a.s.l. in a hypobaric low-pressure chamber situated at the Swiss Aeromedical Center, Dubendorf, Switzerland. Stool samples for the analysis of calprotectin and microbiotal composition, biopsy samples from the rectosigmoid region, and blood samples were repetitively collected and analysed in conjunction with detailed records of clinical symptoms over a subsequent interval of 4 weeks.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• had a diagnosis of Crohn's disease or ulcerative colitis at least 6 months prior to inclusion
• gave written consent
• were in clinical remission (measured by Harvey Bradshaw Activity Index (HBI) in CD and the partial Mayo Score for UC)

Exclusion Criteria:

• had contraindications for a sigmoidoscopy
• had intercurrent bacterial or viral intestinal disease (by culture or serology)
• were pregnant or breast feeding
• had a severe concomitant disease which excluded from participating in the study by means of the study physician
• were likely to or showed no cooperation for the study procedures
• had active infection or systemic antibiotic, antiviral or antifungal treatment 3 weeks before baseline
• were suffering from short-bowel syndrome
• were receiving parenteral nutrition
• had a clinical condition which did not allow a stay at heights of 4,000 m.a.s.l.
• were claustrophobic

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: hypobaric pressure chamber; The healthy volunteers and IBD patients will have a 3-hour exposure to hypoxic conditions simulating an altitude of 4,000 meters above sea level (m.a.s.l.) in a hypobaric pressure chamber. Before and after the pressure chamber sigmoidoscopy will be performed. During stay in the pressure chamber repetitive measurements of bladder volume will be performed by sonography.

Other: hypobaric pressure chamber; hypobaric chamber: ascent within 10 minutes, 3 hour exposure to hypoxic conditions simulating an altitude of 4,000 m.a.s.l., afterwards controlled descent under continuous pulsoximetric control; Other: Sigmoidoscopy; To retrieve biopsies from the colon during the course of the study 3 sigmoidoscopies were performed. The first sigmoidoscopy was performed 1 day before the stay in the hypobaric chamber. The second sigmoidoscopy was performed directly after the hypobaric chamber and the third sigmoidoscopy was performed 1 week after the hypobaric chamber. During each sigmoidoscopy 6 biopsies were taken with standard size forceps (2.4 mm). One biopsy was analysed by real-time quantitative polymerase chain reaction (PCR), one biopsy was analysed by Western blotting and another biopsy was analysed for gene gene-expression by in situ hybridisation. Two biopsies were analysed by immunohistochemistry (IHC) and one biopsy was stained with hematoxylin and eosin (H&E).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Harvey Bradshaw Activity Index (HBI)	Harvey Bradshaw Activity Index (HBI) in Crohn's disease (CD): To calculate the clinical activity of patients with CD the Harvey Bradshaw Activity Index (HBI) was used. This index includes general wellbeing, abdominal pain, the number of bowel movements, abdominal resistance and CD associated extraintestinal diseases. Each category has a point value assigned and from the sum of all categories a point value is calculated.	4 weeks
Change of partial Mayo Score	partial Mayo Score for Ulcerative Colitis (UC): To calculate the clinical activity of patients with UC the partial Mayo Score was used. This clinical index includes the stool frequency, the amount of blood in the stool and the physician rating of disease activity. Each category has a point value assigned from 0 to 3 and from the sum of all categories a point value was calculated. Remission is defined as 0-1 points, mild disease 2-4 points, moderate disease 5-6 points and severe disease as 7-9 points.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in levels of hypoxia-inducible factor (HIF)-1		4 weeks
Change in bladder volume	measured by sonography (ml)	4 weeks
Change in levels of angiotensin and vasopressin in urine		4 weeks
Change in levels of catecholamines (adrenaline and noradrenaline) in blood		4 weeks
Change in pro- and anti-inflammatory cytokins	tumor necrosis factor alpha (TNF-α), tumor necrosis factor (TNF), interleukin-1β (IL-1β), interferon-gamma (IFNg), interleukin-10 (IL-10)	4 weeks
Inflammation in sigmoid colon	Assessed by sigmoidoscopy: signs of inflammation: decreased vascular pattern; ulcers; bleeding	4 weeks

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: University Hospital Inselspital, Berne; University Hospital, Zürich; Triemli Hospital; Zurich Center for Integrative Human Physiology; Institute of Biostatistics; Institute of Physiology Irchel; Institute of Veterinary Physiology; Swiss Aeromedical Center Switzerland; Institute of Experimental Immunology
• Investigators: Principal Investigator: Stephan R Vavricka, Prof. Dr., University of Zurich

Publications and helpful links

General Publications

• Vavricka S, Ruiz PA, Scharl S, Biedermann L, Scharl M, de Valliere C, Lundby C, Wenger RH, Held L, Merz TM, Gassmann M, Lutz T, Kunz A, Bron D, Fontana A, Strauss L, Weber A, Fried M, Rogler G, Zeitz J. Protocol for a prospective, controlled, observational study to evaluate the influence of hypoxia on healthy volunteers and patients with inflammatory bowel disease: the Altitude IBD Study. BMJ Open. 2017 Jan 5;7(1):e013477. doi: 10.1136/bmjopen-2016-013477.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: July 12, 2016
• First Submitted That Met QC Criteria: July 26, 2016
• First Posted (Estimate): July 29, 2016

Study Record Updates

• Last Update Posted (Estimate): July 29, 2016
• Last Update Submitted That Met QC Criteria: July 26, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases
• Other Study ID Numbers: VAV003