RECRUITING: A Clinical Study to Assess the Efficacy and Safety of Gene Therapy for the Treatment of Cerebral Adrenoleukodystrophy (CALD)

Study ALD-104 is an international, non-randomized, open-label, multi-site study in male participants (<or=17 years of age at enrollment) with cerebral adrenoleukodystrophy (CALD). Approximately 35 participants will be infused with Lenti-D Drug Product after myeloablative conditioning with busulfan and fludarabine.

This trial will evaluate the efficacy and safety of autologous cluster of differentiation 34 (CD34+) hematopoietic stem cells, transduced ex-vivo with Lenti-D lentiviral vector, for the treatment of CALD. A subject’s blood stem cells will be collected and modified (transduced) using the Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein. After modification (transduction) with the Lenti-D lentiviral vector, the cells will be transplanted back into the subject following myeloablative conditioning.

RECRUITING: A Clinical Study in Male Pediatric Patients With Cerebral X-linked Adrenoleukodystrophy (cALD) to Assess the Effects of MIN-102 Treatment on Disease Progression Prior to Human Stem Cell Transplant (HSCT) (NEXUS)

An Open-Label, multicenter study in male pediatric patients with cerebral x-linked adrenoleukodystrophy (cald) to assess the effects of MIN-102 treatment on disease progression prior to human stem cell transplant (HSCT).

RECRUITING: National ALD Registry & Biorepository

This is a prospective, non-therapeutic protocol designed to create and maintain a registry of participants with Adrenoleukodystrophy (ALD) and known/presumed carriers of ALD. This study also involves maintaining a prospective biorepository to collect and store buccal swab, blood, stool and urine samples as well. In this protocol, pediatric (including infants), adolescents and adult patients with confirmed or presumed ALD (based on positive VLCFA testing and/or confirmed mutation) will be offered potential study participation. Additionally, presumed carriers of ALD (based on pedigree or confirmed mutation) will be offered potential study participation. After appropriate consent (online or in-person), subjects will be requested to provide a medical history (with authorization of release of medical records), longitudinal biospecimens, and permission to perform laboratory analyses on these samples. The overall goal is to understand the natural disease course in affected and unaffected patients (identified patients and relatives with a diagnosis of ALD), as well as female carriers to assemble a resource of clinical, medical, and biological data from the participants. This study also aims to understand the outcomes of this disease, as well as possibly develop biomarkers to identify prognostic markers for disease progression, which may help develop effective interventions. The biospecimen bank and registry will provide access to samples and data for the ongoing studies as well as will provide an important resource for the future research.

ENROLLING, BY INVITATION: Long-term Follow-up of Participants With Cerebral Adrenoleukodystrophy Who Were Treated With Lenti-D Drug Product

This is a multi-center, long-term safety and efficacy follow-up study for participants with cerebral adrenoleukodystrophy (CALD) who have received Lenti-D Drug Product in a parent clinical study.

After completing a parent clinical study (approximately 2 years), eligible participants will be followed for an additional 13 years for a total of 15 years post-drug product infusion. No investigational drug product will be administered in this study.

NEW, NOT YET RECRUITING: SMART-ALD – A New Lifestyle Intervention to Improve Quality of Life in Women With X-linked Adrenoleukodystrophy (X-ALD)

X-linked Adrenoleukodystrophy (X-ALD) is one of the most frequent inborn error of metabolism caused by mutations in the ABCD1 gene, which codes for the transporter of saturated very long-chain fatty acids (VLCFA) for peroxisomal degradation, thus causing their toxic accumulation in body fluids and tissues. The clinical spectrum ranges from adrenal insufficiency without neurological symptoms to a rapidly progressive, fatal cerebral demyelinating disease that may occur in childhood as well as later in life. The most frequent phenotype in adulthood is adrenomyeloneuropathy (AMN), a slowly progressive myelopathy and peripheral neuropathy, which may also be prevalent in up to 80% of females carrying the X-ALD gene defect. Since signs and symptoms in females are usually milder and with a later onset, they are frequently underestimated, overlooked or misinterpreted, e.g. as Multiple Sclerosis. Consequently, many women with X-ALD do not receive adequate treatment.

Against this background, the development of new therapeutic interventions with the help of eHealth technology (e.g., counselling and treatment via digital communication tools) is of particular relevance, as it provides cost-effective, regular care even for patients who live remote from Leukodystrophy clinics.

The aims of this study is to evaluate the effectiveness of a multi-approach intervention (“SMART-ALD”) on physical and mental well-being and quality of life in n=30 X-ALD symptomatic heterozygous females compared to a waiting list control group (n=30) using electronic health (ehealth) technology.

ACTIVE, NOT RECRUITING: A Pilot Study of Vitamin D in Boys With X-linked Adrenoleukodystrophy

Prior research suggests that higher vitamin D levels in the blood are associated with reduced brain inflammation among individuals with multiple sclerosis, a disease that is similar to the cerebral demyelinating form of ALD. However, serious side effects (e.g. hypercalcemia, kidney stones) can occur if vitamin D levels get too high.

The current study is designed to establish a safe dose of vitamin D for boys with ALD. Although the doses chosen for this study are expected to be safe, the investigators will monitor participants for early signs of vitamin D-related toxicity. The investigators will also examine whether or not vitamin D supplementation affects markers of oxidative stress and inflammation in the blood and brains of ALD boys.

The study requires participants to agree to at least one year of participation. Participants will be asked to take a vitamin D supplement every day, submit blood for analysis every 3 months in the first year, and visit their study center (Stanford University or the Kennedy Krieger Institute) every 6 months throughout the period of study.

Participants will be assigned a vitamin D dose based on bodyweight at entry. Starting doses will include 1,000 or 2,000 international units (IU) of vitamin D3 daily for a 6 month period, followed by a conditional increase to 2,000, 3,000, or 4,000 IU daily thereafter if vitamin D levels have not achieved a target threshold. The vitamin D supplements will be provided by the study. In keeping with the current standard of care for ALD boys aged 18mos – 25 years, participants will need to visit the study site every six months in order to complete a clinic visit and MRI of the brain with gadolinium. As part of this study, however, participants’ will need to submit blood work every 3 months during the first year in order for the study investigators to ensure that the participants’ calcium and vitamin D levels are in a safe range and to study the effects of vitamin D on markers in the blood. The MRI protocol during the first year will also include one additional sequence (magnetic resonance spectroscopy) in order to measure brain metabolites.

The data generated from this study are intended, in part, to help design a future, large-scale clinical trial to determine whether vitamin D supplementation is capable of reducing the risk of developing the cerebral demyelinating form of ALD.

NOT RECRUITING: A Study of the Efficacy and Safety of Hematopoietic Stem Cells Transduced With Lenti-D Lentiviral Vector for the Treatment of Cerebral Adrenoleukodystrophy (CALD)

This trial will assess the efficacy and safety of autologous cluster of differentiation 34 (CD34+) hematopoietic stem cells, transduced ex-vivo with Lenti-D lentiviral vector, for the treatment of cerebral adrenoleukodystrophy (CALD). A participant’s blood stem cells will be collected and modified (transduced) using the Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein. After modification (transduction) with the Lenti-D lentiviral vector, the cells will be transplanted back into the participant following myeloablative conditioning.