Clinical trial NCT02186886: Physiological Intermolecular Modification Spectroscopy (PIMS) in Ulcerative Colitis With Golimumab
Official title: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Ulcerative Colitis
Keywords: Ulcerative Colitis
Golimumab
Physiological Intermolecular Modification Spectroscopy
PIMS
Lead sponsor: Kliniken im Naturpark Altmuehltal
Sponsor class: OTHER
First posted: 2014-07-10
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical response
timeFrame: Week 14
Secondary outcomes:
measure: Calprotectin stool levels
timeFrame: Week 6
measure: Calprotectin stool levels
timeFrame: Week 14
Other outcomes:
measure: molecular spectral range
timeFrame: Week 14
Locations:
city: Kosching
country: Germany
facility: Kliniken im Naturpark Altmuehltal; Klinik Koesching
Study officials:
affiliation: Naturpark Kliniken Altmuehltal
name: Matthias G Breidert, MD
role: PRINCIPAL_INVESTIGATOR
References: