Physiological Intermolecular Modification Spectroscopy (PIMS) in Ulcerative Colitis With Golimumab

Personalised Medicine: a Break Through Approach for Early Determination of Anti Tumor Necrosis Factor (TNF) Responders and Non Responders Among Patients With Ulcerative Colitis in a Prospective Study With Golimumab (Simponi)

Aim of this study is to determine wether the macromolecular spectral characteristic of ulcerative colitis patients - measured by Physiological Intermolecular Modification Spectroscopy (PIMS) - is a predictive factor for response to Simponi treatment

Study Overview

• Status: Unknown
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Golimumab

Detailed Description

It is widely appreciated that almost all proteins and other biological macromolecular in vivo exist, at least transiently, as components of structural and functional complexes. This transient interaction in simple component solutions have been studied using well established daylight light scattering (LS) method which reflects molecular oscillation (7-12). Protein association, protein unfolding, protein aggregation and cellular crowding are known to affect the normal function of cellular system (13-19). In many cases, the resulting small changes in normal protein-protein intra- and intermolecular interactions are thought to lead to a variety of human diseases (20, 21). Based on these and the acquired knowledge on LS, the cutting edge technology, PIMS has been developed. PIMS is a label free technology that is able to study protein-protein and protein-solvent interactions in multi-component solutions. It provides individual real time dynamic fingerprint of total physiological macromolecular assemblies in a tissue in presence and absence of exogenous molecules (drug or drug candidate, peptide or protein).

This technology is based on dynamic molecular resonance of proteins and macromolecules. Cellular extracts in physiological conditions are frozen at -37°C. Macromolecular spectra are registered as the temperature within the sample raises from -37 to 37°C. This provides, within the organ of interest, dynamic fingerprint of an individual entire macromolecular assemblies. The present technology can therefore rapidly and specifically determine the response of a tissue or cell when an exogenous molecule is administrated. It reflects patient molecular capacity to respond to the drugs effect and allows to identifying different subpopulations within a group in response to a specific treatment. It highlights the responders from non-responders to a given treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Kosching, Germany, 85092
    • Recruiting
    • Kliniken im Naturpark Altmuehltal; Klinik Koesching
    • Contact: Matthias G Breidert, MD; Phone Number: 431 +49845671; Email: matthias.breidert@klinik-koesching.de
    • Principal Investigator: Matthias G Breidert, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• moderate to severe active ulcerative colitis
• qualified for initiating Golimumab therapy, i.e.inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine or azathioprine or intolerance of medical contraindications to such therapies
• must be able and willing to provide written informed consent
• must have a negative tuberculosis screening or if inactive (latent) tuberculosis diagnosed anti-tuberculosis therapy to be started before initiation of Golimumab therapy in accordance with local recommendations

Exclusion Criteria:

• cancer
• type one diabetes
• current infection and/or inflammation other than related to ulcerative colitis
• autoimmune diseases
• any contraindications stated by Golimumab product label

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Golimumab; Golimumab: Patients with body weight less than 80 kg initial dose of 200 mg, followed by 100 mg at week 2, then 50 mg every 4 weeks, thereafter // Patients with body weight greater than or equal to 80 kg initial dose of 200 mg, followed by 100 mg at week 2, then 100 mg every 4 weeks, thereafter	Drug: Golimumab; Physiological Intermolecular Modification Spectroscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response	Reduction of partial Mayo Score > 2 points versus baseline	Week 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calprotectin stool levels	Change in calprotectin stool levels at week 6 versus baseline	Week 6
Calprotectin stool levels	Change in calprotectin stool levels at week 14 versus baseline	Week 14

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
molecular spectral range	Change in molecular spectral ranges versus baseline	Week 14

Collaborators and Investigators

• Sponsor: Kliniken im Naturpark Altmuehltal
• Investigators: Principal Investigator: Matthias G Breidert, MD, Naturpark Kliniken Altmuehltal

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (ANTICIPATED): December 1, 2015
• Study Completion (ANTICIPATED): December 1, 2015

Study Registration Dates

• First Submitted: July 1, 2014
• First Submitted That Met QC Criteria: July 9, 2014
• First Posted (ESTIMATE): July 10, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): July 10, 2014
• Last Update Submitted That Met QC Criteria: July 9, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Ulcerative Colitis; Golimumab; Physiological Intermolecular Modification Spectroscopy; PIMS
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Tumor Necrosis Factor Inhibitors; Golimumab
• Other Study ID Numbers: 50831-PIMS-Golimumab-UC