A Phase III Trial of Lorenzo's Oil in Adrenomyeloneuropathy

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DESCRIPTION (provided by applicant): The investigators propose to bring to completion a double-masked placebo controlled study of glyceryl trioleate-glyceryl trierucate (Lorenzo's Oil or LO) therapy in adrenomyeloneuropathy (AMN), the adult form of X-linked adrenoleukodystrophy (X-ALD). AMN is a slowly progressive distal axonopathy that involves the long tracts of the spinal cord and differs from the rapidly progressive inflammatory cerebral forms that most commonly affect boys and adolescents. All forms of X-ALD are associated with the abnormal accumulation of very long chain fatty acids (VLCFA) in plasma and tissues. The oral administration of LO normalizes plasma VLCFA levels within four weeks. While previous therapeutic trials of LO therapy in patients with the cerebral forms of X-ALD has been disappointing, recent studies suggest that it is beneficial in two types of X-ALD: 1) as a preventive of neurological involvement in asymptomatic boys; and 2) in AMN, where it appears to slow the rate of progression. None of the previous studies have been controlled, and the investigators are now conducting the first placebo-controlled trial. The four-year study will include 120 men with AMN who do not have evidence of cerebral involvement, and 120 women who are heterozygous for X-ALD and have an AMN-like syndrome. The study is being conducted at the Kennedy Krieger Institute and the General Clinical Research Center at the Johns Hopkins Medical Institutions. The study was initiated in March 2005 and is coordinated by Westat Inc. Eighty patients have been enrolled, and enrollment will be completed in March 2008. The rate of progression will be compared in the LO and placebo groups using the Kurtzke EDSS score as the primary outcome and a variety of secondary outcomes. A novel part of the study is the utilization and validation of newly developed markers, namely magnetization transfer MRI of the cervical spinal cord and quantitative tests of sensation strength and balance in the motion analysis laboratory. These markers test the structure and function of the parts of the nervous system that are most severely involved in AMN. The studies suggest that they will permit more sensitive and rapid assessment of the rate of progression than can be achieved with current techniques. This would accelerate the evaluation of therapeutic interventions in AMN. These techniques may also be applicable to the study of other spinal cord disorders.