from: http://www.aldfoundation.org/trials_2.html


LORENZO OIL THERAPY TRIAL IN ADRENOMYELONEUROPATHY
PROGRESS REPORT FEBRUARY 15 2006.
(distributed using the Fair Use Act)



Background and Reason for Study

This is a progress report on the Lorenzo Oil Dietary Study for the treatment of Adrenomyeloneuropathy that is now being conducted at the Kennedy Krieger Institute and the General Clinical Research Center at Johns Hopkins Hospital. This study uses Lorenzo Oil, which when combined with reduction of fat intake lowers, and if done carefully, reduces to normal the levels of very long chain fatty acids in the plasma of patients with Adrenoleukodystrophy, including those with the Adrenomyeloneuropathy (AMN) form of the illness. The question is whether lowering of these levels helps patients with AMN.

A preliminary report of Dr Wolfgang Koehler In Germany suggests that it does.. His study involved 45 men with AMN who did not have brain involvement and who were followed for a mean period of 6.7 years (range 2 –12.8 years). Severity of AMN was assessed by the AACS (Adult adrenoleukodystrophy Clinical Scale) a scoring system devised by Drs Koehler and Sokolowski). The mean progression of AACS in the treated patients who had reduced their VLCFA levels to normal was 1.5 AACS units compared to the estimate of 2.6 units who were untreated. Moreover, 22 of the treated patients remained stable, that is the AACS score did not worsen. This important and exciting result is limited because the study was not controlled: The progression of untreated AMN patients is known to vary a great deal, and in this study the progression prior to oil therapy was based on patients‘ historical accounts.

The purpose of the present study is to determine as quickly and accurately as possible whether these preliminary results of the favorable effects of Lorenzo Oil therapy in AMN are sustained. This study uses gold standard “phase 3” study design. That is, it is placebo controlled, Half of the patients will receive the oil half a frequently used dietary oil that does not contain Lorenzo oil but resembles in appearance and taste, and caloric content . The study is “double blinded” Neither the patients or treating personnel know who is receiving the Lorenzo Oil or the placebo. A four year study is planned, Even though patients and treatment staff are “ blinded” as to treatment category, all the data are reviewed by an “unblinded” highly experienced data and safety committee who will review the effect of the therapy continuously and would call for an end of the study if decisive results are obtained before that time.. The study is approved by the FDA and this trial will serve as a key factor in determining whether Lorenzo Oil will become an approved therapy. At present the study is supported financially by the National Institutes of Health, The General Clinical Research Center at John Hopkins Medical Institutions and the Myelin Project.

What does the study mean for the patient who is enrolled?

We will here give a step-by-step account

1. Initial “screening” contact with research nurse ( Kim Hollandsworth) Tel 443 923 2772 E-Mail Hollandsworth@KennedyKrieger.org

For general information and determination of eligibility. The study is designed for men and women with proven diagnosis of ALD, 18 years or older who have mild to severe symptoms of AMN but have still maintained some capacity to walk (still able to walk 20 yards with or without the use of canes or a walker), and who do not have evidence of disease-related changes in the brain on the basis of symptoms and MRI. (Alternate programs for AMN patients who do brain involvement exist in other medical centers with which we collaborate and can make referrals).

2. Two day and admission to the General Clinical Research Center at Johns Hopkins Hospital for studies at the Kennedy Krieger Institute. Arrangements for this are made by the study coordinator (Willy Foreman) and Kim Hollandsworth. The following happens during this busy two day stay:

a. Full explanation of all aspects of the study with opportunity for questions and written consent to participate if the patient agrees.

b. Complete medical and neurological examination by a study physician with assessment of all health problems and other pertinent issues. Based upon this examination the degree of the severity of the AMN will be graded with currently used scoring systems. The Kurtzke Expanded Disability Score (EDSS), the AACS score used by Dr Koehler, and the Multiple Sclerosis Functional Composite Measures. These are the “ Gold Standard” Measures now used world-wide. They will be repeated .at 12, 24, 36 and 48 months and will be the primary measures used to determine the degree to which AMN progresses and whether Lorenzo Oil stops or slows this.

c. Specialized Neuroimaging studies at the F. M. Kirby Center for Functional brain Imaging at the Kennedy Krieger Institute. These are highly specialized non-invasive studies (MRI and Magnetic Resonance Imaging) and a novel technique, magnetization transfer Imaging of the spinal cord which for the first time permits an exact measure of the nerve fiber and myelin abnormality in the spinal cord. We believe that this technique will permit a more precise and rapid way of determining how much damage there is and the degree to which treatment helps.

d. Quantitative measures of strength, sensation. Balance, spasticity and gait in the Motion analysis Laboratory at the Kennedy Krieger Institute. These studies are performed by Dr Katherine Zackowski and her staff. When combined with the Neuroimaging Studies these permit a precise correlation of spinal cord function and structure in AMN which has never been possible before, and, taken together, these provide a sensitive and more rapid way to judge progression of the illness and the effect of treatment.

e. The Somatosensory Evoked response. This non-invasive test measures the speed with which nerve impulses are transmitted in the spinal cord and peripheral nerves.

f. Based upon the results of the assessment of quantitative studies in item d, develop and teach an individualized physical and occupational therapy program. This is provided by MS Jennifer Keller PT in close collaboration with Dr Zackowski, It is offered to all patients. It includes personal demonstration, provision of a videotape and re-adjustment at each of the follow-up visits and telephone and mail contact at regular intervals.

g. Nutrition Program. This key program is provided by Ms Hong Brereton MS, RD, Research Nutritionist at the Johns Hopkins General Research Center. Ms Brereton assesses caloric requirements, develops an diet that provides appropriate calories, fatty acids, minerals and vitamins indivualized to patient preferences, and the amount of the Lorenzo oil or comparison oil. The dosage of the oils is calculated individually by Ms Hong with the advice of a physician medical monitor who knows the therapy status of each patient. The oils are dispensed by the research pharmacy at Johns Hopkins Hospital and mailed to the patients’; homes. Ms Brereton maintains regular phone and mail contact with patients. Patients have maintained their weight and nutritional status. Five of the women participants have lost five to ten pounds, very much in keeping with their desire.

h. Adrenal Function is assessed and followed up by recommendations for adrenal hormone replacement when this is needed.

i. Biochemical Tests. Blood lipids including more than 70 fatty acids, such as very long chain fatty acids, essential fatty acids and polyunsaturated fatty acids are monitored monthly for six months and then every three months. This is important because preliminary results in both adults and in children is obtained only if the VLCFA levels are brought done to normal or near-normal and if deficiencies of essential fatty acids, such as DHA are guarded against.

j. Mutation analysis, that is the nature of the DNA abnormality is defined in each patient.

k. Adverse Event Monitoring. Possible clinical adverse effects are closely monitored/ Complete Blood Count, platelet count. Liver and Kidney Function are monitored at baseline, monthly for six months and at three months intervals thereafter regular telephone contact in regard to any adverse effects is maintained.

Costs:

The Lorenzo Oil, placebo oil, hospital admission and all tests performed during the hospital admissions are provided without cost to the patient

Current Status:

The trial was initiated on March 7 2005. Fifty-two patients
(32 women and 20 men) are now enrolled and 12 additional patients are scheduled.

Additional AMN patients from the US or Canada are invited to join this study.. For more detailed information contact our research nurse, Kim Hollandsworth by E-Mail
(Hollandsworth@KennedyKrieger.org or phone 443 923 2772)

Hugo W. Moser MDH