Research Faces of MLD

The Premier Family Resource for Metachromatic Leukodystrophy Information & Support





Pinterest Follow

DONATE NOW!
Donate Now
Supporting Compassion for families, Awareness, Research, and Education.



Search MLD Foundation



 


Natural History

Quick Links

• New! - Another US Natural History Study opens - (Jan 2014)

• US Natural History Study - Pittsburgh, PA (started 2008).

• FAQ:
  - What is a Natural History Study?
  - What Are the Risks and Concerns of Participating?
  - Why Should My Loved One Participate?
  - etc.

• Comments From the MLD Foundation



A meeting was held in Washington DC in June of 2014 to discuss the MLD Foundation's openNHS Manifesto (OPEN Natural History Study). We are pleased to report that the meeting of industry, researchers, academia, and the MLD Foundation was a success and was very responsive to the issues identified in the Manifesto. An update will be posted on our blog shortly.

We are now recommending participation in the US Natural History study.

Please see the "Comments By the MLD Foundation" section further down this page for more of how we are advocating for patient rights while facilitating more efficient and patient-centric research.


** NEW ** (January 2014)

US Natural History Study Opens (January 2014)

A natural history study targeting 30 late-infantile patients has started recruiting in the US. There are multiple US study sites open (see below).

This is a 2 year study with periodic assessments during the study. The primary endpoint of this study is the change from baseline in motor function using the GMFM (Gross Motor Function Classification assessment). Secondary observations include studying swallowing, nerve conduction, MRI/MRS, CSF, urine, and other biomarkers, and other studies of functioning, cognition, and adaptive behavior.

Inclusion Criteria:

  • Confirmed diagnosis of metachromatic leukodystrophy (by both blood enzyme & urinary sulfatide levels)
  • Under 12 years of age at time of enrollment
  • GMFM-88 total (percent) score greater than or equal to 15 at the screening examination.
  • Complete criteria at ClinicalTrials link below

Exclusion Criteria:

  • History of hematopoietic stem cell transplantation
  • Known or suspected hypersensitivity to agents used for anesthesia or high risk for associated potential complications
  • Enrolled in another clinical study that involves clinical investigations or use of any investigational product (drug or device) within 30 days prior to enrollment in this study or at any time during the study.
  • Patient is 12 years of age or older.
  • Complete criteria at ClinicalTrials link below

SITES – Washington, DC site opened for recruiting January 2014. Los Angeles opened February 2014. Chicago has also opened. Other study sites are anticipated. (see below for contact information)

RISKS/PAIN – This study involves a nerve conduction study, and anesthesia for both a MRI and lumbar puncture/spinal tap.
IMPORTANT ==> Please see the note below about anesthesia and the risks/pain associated with the additional studies.

ELIGIBILITY or STUDY QUESTIONS –Please see the note below about anesthesia. Please feel free to email us or phone the MLD Foundation to ask questions about this study and your loved one's eligibility to participate. We are happy to help you engage with the study coordinators.

TRIAL SITE CONTACTS
– Amy Pizzino myelindisorders@childrensnational.org – Children's National Medical Center, Washington DC. Principal InvestigatorAdeline Vanderver, MD

– Carmen Sanchez carmensanchez@labiomed.org – Harbor UCLA Pediatrics, Torrance (Los Angeles), CA. Principal Investigator: Patricia Dickson, MD

CLINICALTRIALS.GOV
Trial ID NCT01963650



US Natural History Study – Pittsburgh (2012)

A natural history study primarily targeting late-infantile patients s now closed (1/14).

This is a 2 year study with periodic assessments during and after the study. The primary endpoint of this study is changes from baseline in Neurodevelopmental tests with audiology and MRI being studied as secondary outcomes. Genetic and biochemical testing is part of this study.

Inclusion Criteria:

  • Confirmed diagnosis of metachromatic leukodystrophy (by both blood enzyme & urinary sulfatide levels)
  • Under 6 years of age at time of enrollment, with symptom onset prior to age 4.
  • Patient must have voluntary function (as judged by the investigator), including cognitive and motor function that is no more than 3 standard deviations below normal at the time of enrollment.
  • Complete criteria at ClinicalTrials link below

Exclusion Criteria:

  • History of hematopoietic stem cell transplantation
  • multiple sulfatase deficiency
  • Enrolled in another clinical study that involves clinical investigations or use of any investigational product (drug or device) within 30 days prior to enrollment in this study or at any time during the study.
  • Patient is 6 years of age or older.
  • Complete criteria at ClinicalTrials link below

SITES – University of Pittsburgh, Pittsburgh Pennsylvania USA. No other study sites are anticipated.

RISKS/PAIN – This study involves anesthesia for MRI and a lumbar puncture/spinal tap.
IMPORTANT ==>
Please see the note below about anesthesia and the risks/pain associated with the additional studies.

ELIGIBILITY or STUDY QUESTIONS –Please see the note below about anesthesia. Please feel free to email us or phone the MLD Foundation to ask questions about this study and your loved one's eligibility to participate. We are happy to help you engage with the study coordinators.

TRIAL CONTACT – Sarah Evans, BA 412-692-6350 sarah.evans@chp.edu or Tara West, CPNP (412) 692-6352 tara.west@chp.edu – University of Pittsburgh, Children's Hospital of Pittsburgh - UPM, Pittsburgh, Pennsylvania, USA.

Principal InvestigatorMaria L Escolar, MD University of Pittsburgh, Children's Hospital of Pittsburgh - UPM, Pittsburgh, Pennsylvania, USA.

ClinicalTrials.gov – Trial ID NCT00639132

HISTORY: Originally launched in 2008 by Zymenex, taken over by Shire HGT in 2009, UNC Chapel Hill in 2010, and then by Program for the Study of Neurodevelopment in Rare Disorders at the University of Pittsburgh on 11/9/2012 where the inclusion age was expanded from <5 years old to <6 years old and recruiting was temporarily halted. In July of 2013 recruiting was re-opened and they started collecting DNA samples.


FAQ - Questions About Natural History Studies

NHS = Natural History Study

What is a Natural History Study?

A NHS is a study of patients who have not had any disease modifying therapies to see the "natural" progression of the disease. These studies are important to better understand the disease and to provide a baseline by which disease modifying therapies can be compared.

What Is Required?
Your loved one must meet the inclusion/exclusion criteria and you must be willing to participate in the periodic assessments throughout the study to capture the disease progression. Typically, all medical expenses related to the study are paid, but travel and lodging may not be covered - check the study details to be sure.

Will My Loved One Benefit From Participating?
Generally there is no direct quality of life or medical benefit since a NHS is observational, not a therapy. However, in some cases, and depending on the study center you choose and the staff at that center, participating in a NHS may give you direct access to disease experts that you might not otherwise be able to access. This might result in advice and guidance that could improve your loved one's quality of life.

Will It Hurt? What Are the Risks?
Most studies use MRI to observe changes in the brain over time. MRI's typically involve a general anesthesia to relax the patient and help them hold still. Please see the comments below about reported risks and recommendations for anesthesia.

Some studies require a spinal tap (lumbar puncture) to study the cerebrospinal fluid (CSF). There may be some minor pain, some risk of infection, and a post-puncture headache associated with the procedure.

Studies may also involve muscle biopsies and nerve conduction studies. A muscle biopsy involves using a needle or a small incision to remove a small amount of muscle tissue under a local anesthetic. A nerve conduction study uses electrical stimulus to measure how quickly the signal travels down a MLD-damaged nerve. Local short acting anesthetics are generally fine but we still recommend as low a dose as practical. There can be some temporary localized pain with both of these procedures.

Most of the other studies are behavioral or observational and do not have any notable risks or pain.

ANETHESIA – Reported Risks and Recommendations <== IMPORTANT

For all anesthesia we recommend as low a dose of as fast acting an anesthetic for as short a period of time as possible.

We do not hear reports of problems from local anesthesias, such as used for a biopsy or to place a G-tube.

However, anecdotal reports from some families report symptom progression after general anesthesia. As a result, we suggest as low a dose of as fast acting an anesthetic for as short a period as possible. We strongly suggest you avoid gas anesthesia and instead recommend a short acting IV form instead. Your anesthesiologist may not have seen a MLD patient before so it is important to communicate with him/her several days before the procedure to discuss and perhaps influence their plans. Families report success suggesting a technique similar to what might used for a MS or brain injury patient.

As always, we must remind you that we are not doctors and are not dispensing medical advice. Always consult your local medical care team before making any procedure or therapy decisions.

Why Should My Loved One Participate?
Participating in a NHS helps researchers develop therapies. Without these studies the disease would be less well understood and it would be more difficult to draw scientific conclusions about the effectiveness of a proposed therapy. The FDA and EMA require this scientific analysis to approve new therapies so NHS are generally required of every disease as therapies are developed.


Comments By The MLD Foundation on Natural History Studies

We recommend patients only participate in medical studies only after knowing the study is both collaborative and there is future open access to the study data for other researchers. Properly designed studies will protect your privacy while facilitating longevity in MLD research.

There have historically been Natural History Studies involving extensive patient effort where the data was used for one study, siloed (isolated), and not made openly available for future researchers. We have also seen situations where the method of data gathering, the scope of the data gathered, or the patient consents given when the study was started precluded the use of the data for other research projects.

We're speaking out and advocating that these sort of wasteful and proprietary uses of the MLD patient community cease.

Supportive of Studies
The MLD Foundation is fully supportive of Natural History Studies and recognizes the need for these studies to better understand, characterize, and treat the disease. Further, we realize the scientific requirements for FDA/EMA approval of clinical trials and new therapies requires a baseline of untreated progression to compare the therapies to and to establish research end points.

We also fully realize these studies can be painful and might carry some medical risk so the commitment of MLD families to participate should not be taken lightly.

It is because of this pain and risk we want to make sure these studies are conducted in ways that are collaborative, as comprehensive as possible, and the data is captured, stored, and shared in a manner that allows the data to be openly used in future research.

Longevity, Sharing, and Use of NHS Data – Since gathering NHS data requires significant time, funding, effort by families, and carry the potential for pain with some disease progression risk, the MLD Foundation feels very strongly the raw and analyzed data be made available to all future researchers. We respect the study funder may want exclusive or prioritized rights to the data ... but these desires can be honored in a way that meets their short term goals, enables future research, and is respectful to the MLD patient community . We not only request that NHS data be made available, we are vocal advocates to this end, and we are willing to provide resources to continue to make the data available to future researchers after the funding organization(s) usually shorter-term interests are achieved. Sometimes there are IP or proprietary data concerns that must be addressed –  we will work hard to resolve these concerns in a manner that is fair to the funding organizations(s) and the MLD patient community.

Registries & Data Repositories – In December 2013 the MLD Foundation was selected as one of 10 advocacy organizations to benefit from a $1M PCORI grant to launch a disease registry that will form the basis for a patient driven advocacy organization managed independent registry serving all researchers in all countries for future projects. We are building this registry in a way that is sustainable, expandable, honors patient privacy, has extensive data use consent capabilities, and can host a mix of patient reported, scientifically gathered, medical health record, and researcher contributed data.

We are putting our efforts and funds into this project to advance, expedite, and hopefully cost reduce future therapy development.

 

Home | About Us | Contact Us | Disclaimer | Privacy Policy | Legal-Trademarks |(c) 2000-2014 MLD Foundation