Mitochondrial Dysfunction and Disease Progression

NCT02549703 | Completed

• 2 other identifiers: GCO 14-1495CDMRP-MS140072
• Study Type: observational
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

While the last several years have seen great strides in the treatment of relapsing forms of MS, progressive MS, responsible for the majority of MS-related disability, lags far behind. Despite much research, the lack of understanding related to what causes patients' relentless decline in function results in an inability to develop targeted treatment strategies suitable for clinical trials. This grant has two main goals. The first goal is to extend the investigators preliminary study on rat neurons treated with the CSF of MS patients to a larger number of Progressive patients in order to validate the initial findings and extend the study to include analysis of human neurons. The initiating PI (Dr. Casaccia) and the Partnering PI and Clinical Neurologist (Dr. Katz Sand) have recently identified components that are present in the CSF of progressive patients that impair the ability of rat neurons to produce energy. The partnering PI, Dr. Quinzii (Columbia University) together with collaborator Dr. Fossati (NY Stem Cells Foundation), have characterized human neurons generated from stem cells derived from skin biopsies of progressive patients and detected the presence of energetic deficits. The experimental plan will build on these results and test hypotheses of disease progression. The overall goal is to improve understanding on how to stop neurons from degenerating and stop clinical progression. The second goal is to ask whether it is possible to define a progressive disease course on the basis of combined biochemical, functional and imaging measurements. The initiating PI will be responsible for the biochemical assessment of CSF and serum samples and, together with partnering PI Quinzii, will also provide functional bioassays measurements of mitochondrial bioenergetics impairment in patients. These data will be combined with clinical assessment and MRI evaluations conducted by the partnering PI Katz Sand and collaborator Inglese. A two year clinical and imaging follow up from the initial recruitment will allow to define whether the combined measurements can be used by clinical neurologists to define the disease course and better identify therapeutic options for patients. The expectation is that the completion of the stated aims of research will allow an advancement of the current knowledge of the progressive form of MS and lead to potential new therapeutic targets.

Conditions

Clinically Isolated Syndrome; Relapsing-Remitting Multiple Sclerosis; Secondary Progressive Multiple Sclerosis; Primary Progressive Multiple Sclerosis

Keywords

multiple sclerosis; progressive multiple sclerosis; mitochondria; neurodegeneration

Outcome Measures

Primary Outcomes (2)

• Spare respiratory capacity

  Mitochondrial bioenergetic measurements

  2 years

• Oxygen consumption rate

  Mitochondrial bioenergetic measurements

  2 years

Secondary Outcomes (4)

• Multiple Sclerosis Functional Composite (MSFC) Score

  1 year

• Multiple Sclerosis Functional Composite (MSFC) Score

  2 years

• Expanded Disability Status Scale

  2 years

• MS Impact Scale-29 (MSIS-29)

  2 years

Study Arms (3)

Relapsing Remitting Multiple Sclerosis

Patients with Relapsing Remitting Multiple Sclerosis/Clinically Isolated Syndrome

Secondary Progressive Multiple Sclerosis

Primary Progressive Multiple Sclerosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Multiple sclerosis patients willing and able to undergo the assessments required for this study.

You may qualify if:

• male and female subjects age 18 or older
• diagnosis of one of the following:
• RRMS according to McDonald 2010 criteria or a diagnosis of CIS with clinical symptoms and MRI consistent with MS
• PPMS according to McDonald 2010 criteria
• SPMS defined as at least six months of progressive decline following an initial relapsing disease course
• able and willing to undergo clinical evaluation, MRI, lumbar puncture, and skin biopsy and to return for follow up assessments at the end of year 1 and year 2
• able and willing to provide informed consent.

You may not qualify if:

• pregnancy
• inability to undergo lumbar puncture, due to anticoagulant therapy that cannot be held for the day of the procedure or results of screening laboratory testing or the presence of another medical condition that would render the procedure unsafe, as determined by the investigator
• inability to undergo MRI, due to the presence of metallic implants incompatible with MRI or any other reason
• presence of other severe medical conditions likely to influence study results or that raise the likelihood of harm to the patient as a result of study participation, as determined by the investigator (e.g. the presence of a brain mass, which could influence the CSF results and also might make lumbar puncture unsafe)
• inability to complete the protocol for any reason

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• Columbia University: collaborator
• New York Stem Cell Foundation Research Institute: collaborator

Study Sites (1)

Icahn School of Medicine

New York, New York, 10029, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood and CSF samples will be stored indefinitely at the Casaccia lab. Skin samples will be stored indefinitely at the New York Stem Cell Foundation.

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis; Nerve Degeneration

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ilana Katz Sand, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2015
• First Posted: September 15, 2015
• Study Start: September 1, 2015
• Primary Completion: September 27, 2018
• Study Completion: September 27, 2018
• Last Updated: February 20, 2019

Record last verified: 2019-02

Locations

US (1)