The Effect of Alemtuzumab on the Blood-brain-barrier and the Brain's Metabolism in Multiple Sclerosis Patients

NCT03193086 | Unknown FDA Drug

• 1 other identifier: GZ-2016-11629
• Study Type: observational
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The development and progression of multiple sclerosis seem to be driven by concomitant inflammation and, to a less well-defined degree, disturbances in metabolism of individual cells of the human central nervous system as well as changes in the dynamical supply of blood to the brain. These alterations in normal physiology can be quantified by investigating the change in specific parameters over the time course of multiple sclerosis evolution. Amongst these specific parameters, the ability of the so-called blood-brain-barrier to selectively filter nutrients from the blood stream prior to passage into the nervous tissue, is disrupted in multiple sclerosis, and the severity of this deficiency seem to be related to the underlying disease burden. The present study utilises a novel imaging technology in order to monitor changes in the integrity of the blood-brain-barrier over the course of treatment with a biological disease modifying agent known as alemtuzumab. Alemtuzumab is a potent immunosuppressant drug. It is hypothesised that alemtuzumab reverts the deficiency in blood-brain-barrier integrity and, conversely, the severity of blood-brain-barrier disruption at several time points during alemtuzumab treatment can be utilised as prognostic marker for the requirement of additional administration of alemtuzumab beyond the regular treatment regimen. In addition, several other factors are investigated by advanced imaging techniques in combination with blood and urine samples in order to elucidate the possible underlying mechanism of alemtuzumab efficacy. It is hypothesized that alemtuzumab normalises metabolic alterations and changes in the blood supply through resolution of inflammation in the brains of multiple sclerosis patients.

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis; Blood-Brain-Barrier; Treatment response; Metabolism; Alemtuzumab; Perfusion; Oxygen consumption

Outcome Measures

Primary Outcomes (1)

• Blood-Brain-Barrier Permeability

  Blood-Brain-Barrier Permeability as measured by Dynamic-Contrast-Enhanced MRI (DCE-MRI)

  1 year

Secondary Outcomes (9)

• Oxygen Consumption

  1 year

• Cerebral perfusion

  1 year

• Diffusion Tensor MRI parameters and MR spectroscopy metabolite concentrations

  1 year

• Brain atrophy

  2 years

• Clinical Severity of Disease

  1 year

Study Arms (1)

Alemtuzumab treated MS patients

Those with Multiple Sclerosis that have commenced therapy with alemtuzumab (60 mg infusion over the course of 5 days) and completed treatment with alemtuzumab (additional 36 mg infusion during the course of 3 days, 12 months later).

Drug: Alemtuzumab

Interventions

Alemtuzumab DRUG

Alemtuzumab is administered to eligible patients in accordance with established treatment regimes. Initially 60 mg of alemtuzumab is injected intravenously over the course of 5 days. The first treatment series is followed by the injection of 36 mg of alemtuzumab over the course of 3 days 12 months later. During both drug interventions, the transient exacerbation in disease severity is alleviated by concomitant steroid therapy.

Also known as: Lemtrada

Alemtuzumab treated MS patients

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients are recruited from the two dedicated MS clinics in the secondary health care sector of the danish capital region.

You may qualify if:

• A diagnosis of Relapsing-Remitting Multiple Sclerosis
• Eligible for alemtuzumab treatment at Glostrup Hospital or The Danish Kingdom Hospital
• Subjects must be deemed physically and mentally able to participate in the study

You may not qualify if:

• Contraindications to MRI scanning (pregnancy, pacemakers, claustrophobia, extreme obesity)
• Contraindications to the use of MRI contrast agents (kidney disease, previous allergic reactions)
• Conflicting disorders (e.g. disorders with a systemic, inflammatory component)

Sponsors & Collaborators

• Glostrup University Hospital, Copenhagen: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

Functional Imaging Unit, Department of Clinical Physiology, Nuclear medicine and PET, Glostrup Hospital

Glostrup Municipality, Copenhagen Capital Region, 2600, Denmark

RECRUITING

Related Publications (17)

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  PMID: 12045719 BACKGROUND

• Cramer SP, Larsson HB. Accurate determination of blood-brain barrier permeability using dynamic contrast-enhanced T1-weighted MRI: a simulation and in vivo study on healthy subjects and multiple sclerosis patients. J Cereb Blood Flow Metab. 2014 Oct;34(10):1655-65. doi: 10.1038/jcbfm.2014.126. Epub 2014 Jul 30.

  PMID: 25074746 BACKGROUND

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• Cramer SP, Modvig S, Simonsen HJ, Frederiksen JL, Larsson HB. Permeability of the blood-brain barrier predicts conversion from optic neuritis to multiple sclerosis. Brain. 2015 Sep;138(Pt 9):2571-83. doi: 10.1093/brain/awv203. Epub 2015 Jul 17.

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  PMID: 18594554 BACKGROUND

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  PMID: 2255233 BACKGROUND

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• Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Skoromets A, Stolyarov I, Bass A, Sullivan H, Margolin DH, Lake SL, Moran S, Palmer J, Smith MS, Compston DA. Alemtuzumab more effective than interferon beta-1a at 5-year follow-up of CAMMS223 clinical trial. Neurology. 2012 Apr 3;78(14):1069-78. doi: 10.1212/WNL.0b013e31824e8ee7. Epub 2012 Mar 21.

  PMID: 22442431 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma, urine

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Alemtuzumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Henrik BW Larsson, MD, Prof.

  Functional Imaging Unit, Department of Clinical Physiology, Nuclear medicine and PET, Glostrup Hospital

  STUDY DIRECTOR

Central Study Contacts

Peter F Svane, MD

CONTACT

93906653; peter.frederiksen.svane@regionh.dk

Stig P Cramer, MD, PhD

CONTACT

38634624; stig.praestekjaer.cramer@regionh.dk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: June 14, 2017
• First Posted: June 20, 2017
• Study Start: January 1, 2017
• Primary Completion: March 31, 2020
• Study Completion: March 31, 2020
• Last Updated: June 20, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)