Trials of Idebeone in Progressive MS.

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For those of you interested in studies aimed at PPMS, there are clinical trials (NCT00950248) are being performed in Progressive MSers

Idebenone is a drug developed as a synthetic analog of coenzyme Q10 (CoQ10) which is an ant-oxidant that was originally targeted to congnitive behaviour therapy.

Objective: The goal of this study is to assess the safety,
therapeutic efficacy and mechanism of action of idebenone in
primary-progressive multiple sclerosis (PP-MS) patients.

Study Population: Adult, untreated patients with PP-MS with
disability ranging from none to moderately severe will be included in
the trial. The upper age limit in this study has been set at 65; setting
an age limit should permit us to focus on the potential neuroprotective
effect of idebenone in PP-MS and limit the confounding factor of the
natural aging process and its known negative influence on
neuro-regeneration. Published data indicate that higher doses (10-50
mg/kg) of idebenone per day are required for beneficial effects on
neurological disability in comparison to the lower doses (5-10mg/kg)
that are sufficient for beneficial effects on cardiac/systemic functions
in Friedreich’s ataxia (FRDA) patients. Therefore, in order to target
the CNS compartment, we will use a daily dose of 2250mg (750mg 3 times
per day), which will provide target values of 10-50mg/kg for virtually
all adult patients.

Design: This is a Phase I/II safety/efficacy trial with an
adaptive trial design: one year of pretreatment baseline period serves
the dual purpose of collecting patient-specific biomarkers of disease
progression and collecting longitudinal neuroimaging and clinical data
for selection of primary outcome measures. This baseline period is then
followed by a double-blind, idebenone versus placebo treatment phase for
a total of 2 years. Based on preliminary sample size estimates, current
enrollment calls for a total of 66 patients (33 per arm). Outcome
Measures: Quantitative neuroimaging measures of central nervous system
(CNS: i.e. brain and spinal cord) tissue destruction and clinical and
functional (i.e. electrophysiological) measures of neurological
disability will be collected every 6-12 months. Additionally, biomarkers
focusing on analysis of reactive oxygen species (ROS) and oxidative
stress will be collected every 12 months. The trial is currently powered
using progression of brain atrophy as detected by SIENA methodology as
the primary outcome measure. However, this may not be the most sensitive
outcome available. In recognition of this, the trial has an adaptive
design: i.e. it incorporates analysis of progression of CNS tissue
destruction as measured by quantitative MRI markers and
clinical/paraclinical markers defined as secondary outcome measures in
the first 30 enrolled patients during the one year pre-treatment
baseline, before randomization.



Ages Eligible for Study: 18 Years to 65 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
INCLUSION CRITERIA:
PP-MS as determined by the 2005 modification of McDonald’s diagnostic criteria
Age from 18-65 years (inclusive)
EDSS measure of neurological disability from 1 (no disability, clinical signs only) to 7 (ambulatory with bilateral support)
Able to provide informed consent
Willing to participate in all aspects of trial design and follow-up
If able to become pregnant or to father a child, agreeing to commit to the use of a reliable/accepted method of birth control (i.e. hormonal contraception (birth control pills, injected hormones, vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom with spermicide) or surgical sterilization (hysterectomy, tubal ligation, or vasectomy in a partner)) for the duration of treatment arm of the study
Not receiving any immunomodulatory/immunosuppressive therapies for a period of at least 3 months before enrollment in the study
No exposure to idebenone, coenzyme-Q(10) or other dietary supplements (such as antioxidants, mitochondrial-function promoting supplements or vitamins in excess of 3 times recommended daily doses) for a period of at least 1 month before enrollment in the study

EXCLUSION CRITERIA:
Alternative diagnoses that can explain neurological disability and MRI findings
Clinically significant medical disorders that, in the judgment of the investigators, could cause CNS tissue damage or limit its repair, or might expose the patient to undue risk of harm or prevent the patient from completing the study
History of hypersensitivity reaction to idebenone or coenzyme-Q
Pregnant or lactating women. All women of child-bearing potential must have a negative pregnancy test prior to the medication phase of the study.
Abnormal screening/baseline blood tests exceeding any of the limits defined below:

i. Serum alanine transaminase or aspartate transaminase levels greater than 3 times the upper limit of normal values
ii. Total white blood cell count < 3,000/mm(3)
iii. Platelet count < 85,000/mm(3)
iv. Serum creatinine level > 2.0 mg/dl or eGFR (glomerular filtration rate) < 30
v. Positive pregnancy test
Patients who are receiving any immunosuppressive therapies (including cytostatic agents) due to the concern that these drugs may contribute to neurodegeneration or limit CNS repair

Please refer to this study by its ClinicalTrials.gov identifier: NCT00950248

Contacts
Contact: Joan M Ohayon, C.R.N.P. (301) 496-0064 ohayonj@ninds.nih.gov
Contact: Bibiana Bielekova, M.D. (301) 496-1801 bielekovab@mail.nih.gov

CoI None 





About the author

MouseDoctor

7 comments

  • "For those who are always complaining about not enough being done for PPMS."

    I think complaining is the wrong term – I'd complain if the coffee I ordered turned up cold.

    If you ever get to meet someone with advanced PPMS, you'd understand why many would prefer to be dead. After 50+ years of research, the researchers still can't tell us what is driving progressive MS, or offer up any treatment that is even mildly effective. Would you like to watch your body / functions disintegrate (no more head-banging to Thin Lizzy)? It's a grim disease and given that research has failed us so far, I think we're entitled to feel pretty hacked off.

  • Forgive me if don't do a happy dance at the news of receiving the crumbs from the table.I would suggest it will take more than one or two studies into progressive MS before you can convince this cynic at least, that you understand why it appears MS progresses despite any correlation to relapses. Sorry if you think pw ppms shouldn't complain, but the tone of your opening sentence really does say more about you than I think you realise.

  • Shame on you MouseDoctor for having that tone towards us PPMSers.

    I don't think anyone one of us doubts that efforts are being made to find out more about our disease but the lack of real prgress is woeful.

    The only thing we can do is complain and fight for better access to improve our lives. We are left at the margins, progressively getting worse while neuros scrath their heads in confusion and apathy.

  • I think it's a bit much to slag off Mouse Doc for his comment.

    What is interesting is the scientific rationale behind choosing Idebenone to test on PPMS. It stimulates the mitochondria, but – unlike CQ10 – can cross the Blood Brain Barrier.

    A recent post suggested that Modafinil in people with RRMS delayed disability. The authors suggested that it halved the development rate of progression in PPMS.

    Perhaps modafinil and idebenone have a similar action? This article poses a theory: "The mitochondrion is the biggest producer of reactive oxygen species in the cell, and as such modafinil may target this organelle to directly inhibit free-radical production and promote ATP production, which would tend to promote increases in creatine-phosphocreatine production. "

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654794/

    If I had PPMS (or SPMS) I'd try Modafinil and Idebenone. I have RRMS and take both.

  • I did not write the post but did publish it so carry the can. If there was offence caused I apologise on behalf of myself and the author.

    This was not the intention but we do take a lot of stick when it comes to PPMS.

    This will no doubt not change until something is found to be active. This post shows that it is high on the agenda..although I agree you do not feel that it is.

    Our opinion as ever is that one should wait until the agents are shown to work in clinical trials and that they are safe

By MouseDoctor

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