Ignite Creation Date:
2024-10-25 @ 8:04 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06513533
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-07-17
Brief Title:
Dimethyl Fumarate in Adrenomyeloneuropathy
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Effect of Dimethyl Fumarate Administered to Patients With Adrenomyeloneuropathy a Multicenter Placebo Controlled Phase IIbIII Trial
Status:
RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this clinical trial is to determine if dimethyl fumarate is effective in treating motor problems in adults with Adrenomyeloneuropathy The trial will also assess the safety of dimethyl fumarate and explore the molecular mechanisms underlying the disease The primary questions it aims to answer are
Does dimethyl fumarate improve motor problems in participants
What medical issues do participants experience while taking dimethyl fumarate Researchers will compare the effects of dimethyl fumarate to a placebo a substance that looks like the drug but contains no active ingredients to evaluate its effectiveness in treating Adrenomyeloneuropathy
Participants will
Take either dimethyl fumarate or a placebo daily for 36 months
Visit the clinic at the start of the trial then at 3 months 6 months and every 6 months thereafter for checkups and tests
Does dimethyl fumarate improve motor problems in participants
What medical issues do participants experience while taking dimethyl fumarate Researchers will compare the effects of dimethyl fumarate to a placebo a substance that looks like the drug but contains no active ingredients to evaluate its effectiveness in treating Adrenomyeloneuropathy
Participants will
Take either dimethyl fumarate or a placebo daily for 36 months
Visit the clinic at the start of the trial then at 3 months 6 months and every 6 months thereafter for checkups and tests
Detailed Description:
Adrenoleukodystrophy X-ALD is the most prevalent rare genetic disorder affecting the brains white matter It is caused by mutations in the ABCD1 gene which encodes a transporter involved in the degradation of very long-chain fatty acids VLCFA As a result VLCFA accumulate in tissues and plasma serving as a pathognomonic biomarker for diagnosis The disease manifests in two main forms i adrenomyeloneuropathy AMN characterized by chronic progressive spastic paraplegia due to distal axonopathy and ii cerebral ALD cALD a rapidly progressing and fatal demyelinating leukodystrophy Current therapeutic options are inadequate limited to bone marrow transplants and gene therapy for patients with cerebral inflammation No treatment is available for AMN which affects 60 of patients
We have discovered that excess VLCFA leads to mitochondrial reactive oxygen species ROS production and oxidative damage a major factor driving pathogenesis More recently we found that the main endogenous response to oxidative damage the NRF-2 pathway is impaired in X-ALD Preclinical tests with an NRF2 activator specifically the current treatment for multiple sclerosis dimethyl fumarate DMFTecfidera showed promising results All major molecular and cellular pathogenic mechanisms were restored including i mitochondrial function and biogenesis ii redox homeostasis iii bioenergetic failure iv neuroinflammation along with axonal damage and clinical signs of the disease such as locomotor disability Consequently we obtained an international patent for repurposing DMF for X-ALD US15957601 and Orphan Drug Designation by the EMA in 2020 EMAOD0000010028
Now we are translating this knowledge into a randomized phase IIbIII double-blind placebo-controlled study over 36 months for 40 AMN patients to determine if DMF is effective in these patients For the first 24 months patients will be divided into two groups placebo and active treatment in a ratio of 12 A 12-month extension phase will follow during which all patients will receive treatment Furthermore we aim to elucidate the molecular mechanisms driving the disease and dissect the redox-inflammatory effects of DMF using an integrative multi-omics approach which will involve single-cell RNA sequencing in PBMC and lipidomics in plasma The clinical and molecular data from historical national and international AMN and cALD cohorts will be pooled to identify markers of severity and progression Our goal is to address unmet needs in AMN while generating novel fundamental knowledge that will be useful for this and other common axonopathies
We have discovered that excess VLCFA leads to mitochondrial reactive oxygen species ROS production and oxidative damage a major factor driving pathogenesis More recently we found that the main endogenous response to oxidative damage the NRF-2 pathway is impaired in X-ALD Preclinical tests with an NRF2 activator specifically the current treatment for multiple sclerosis dimethyl fumarate DMFTecfidera showed promising results All major molecular and cellular pathogenic mechanisms were restored including i mitochondrial function and biogenesis ii redox homeostasis iii bioenergetic failure iv neuroinflammation along with axonal damage and clinical signs of the disease such as locomotor disability Consequently we obtained an international patent for repurposing DMF for X-ALD US15957601 and Orphan Drug Designation by the EMA in 2020 EMAOD0000010028
Now we are translating this knowledge into a randomized phase IIbIII double-blind placebo-controlled study over 36 months for 40 AMN patients to determine if DMF is effective in these patients For the first 24 months patients will be divided into two groups placebo and active treatment in a ratio of 12 A 12-month extension phase will follow during which all patients will receive treatment Furthermore we aim to elucidate the molecular mechanisms driving the disease and dissect the redox-inflammatory effects of DMF using an integrative multi-omics approach which will involve single-cell RNA sequencing in PBMC and lipidomics in plasma The clinical and molecular data from historical national and international AMN and cALD cohorts will be pooled to identify markers of severity and progression Our goal is to address unmet needs in AMN while generating novel fundamental knowledge that will be useful for this and other common axonopathies
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None