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

Sponsor

Kliniken im Naturpark Altmuehltal (Other)

Overall Status

Unknown status

CT.gov ID

NCT02186886

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis	Drug: Golimumab	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

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 Start Date :

Jun 1, 2014

Anticipated Primary Completion Date :

Dec 1, 2015

Anticipated Study Completion Date :

Dec 1, 2015

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Clinical response [Week 14]
Reduction of partial Mayo Score > 2 points versus baseline

Secondary Outcome Measures

Calprotectin stool levels [Week 6]
Change in calprotectin stool levels at week 6 versus baseline
Calprotectin stool levels [Week 14]
Change in calprotectin stool levels at week 14 versus baseline

Other Outcome Measures

molecular spectral range [Week 14]
Change in molecular spectral ranges versus baseline

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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