Adrenomyeloneuropathy MedDRA version: 20.0 Level: LLT Classification code 10069075 Term: Adrenomyeloneuropathy without cerebral involvement System Organ Class: 100000004850
Conditions
Interventions
Trade Name: Albunorm® 5%,
Product Name: Albumin
Pharmaceutical Form: Solution for solution for infusion
INN or Proposed INN: ALBUMIN
Other descriptive name: ALBUMIN
Concentration unit: millilitre(s)/k
Sponsors
Aurora Pujol Onofre
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Men of 18 to 65 years old, inclusive 2. Elevated plasma VLCFA and gene mutation identified 3. Clinical signs of AMN with at least pyramidal signs in the lower limbs and difficulties to run 4. Presence of motor deficit according to the EDSS scale 5. Ability to perform the 2MWT 6. Normal brain MRI or brain MRI showing the following abnormalities that can be observed in AMN patients without cerebral form of X-ALD, obtained in the 6 months prior to screening: •abnormal hyperintensity of pyramidal tract fibers in the brain stem on FLAIR or T2 sequence •abnormal hyperintensity of pyramidal tract fibers in the internal capsules on FLAIR or T2 sequence •cerebellar atrophy •moderate cortical atrophy 7. Appropriate steroid replacement if adrenal insufficiency is present 8. Signed Informed consent 9. Affiliated to the Spanish Public Health System Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Any contraindication for plasma exchange due to behavioral disorders or abnormal coagulation parameters, such for example: - Hypocalcemia (Ca++ 1.5) - Beta-blocker treatment and bradycardia 2 mg/dl 7. Uncontrolled high blood pressure (systolic blood pressure of 160 mmHg or higher and/or diastolic blood pressure of 100 mmHg or higher despite regular treatment during the last 3 months) 8. Liver cirrhosis or any liver problem with GPT > 2.5 x ULN, or bilirubin > 2 mg/dl 9. Heart diseases as evidenced by myocardial infarction, severe or unstable angina, or heart failure in the past 12 months 10. Gadolinium enhancement on T1 sequence of any abnormal hypersignal of white matter, including myelinated pyramidal tracts, visible at brain MRI on FLAIR sequences 11. Significant peripheral edema (2+ or more on the Assessment Chart for Pitting Edema) of the extremities of any etiology 12. Any evolutive malignancy during the last five years or any condition complicating adherence to the study protocol 13. Smokers (one pack/ day or more for at least 20 years), current or former 14. Any psychiatric disease 15. Present participation to another therapeutic clinical trial for X-ALD, or the receipt of any other investigational drug in the three months prior to the start of the study 16. Patients being treated with anticoagulants or antiplatelet therapy 17. Not easily contactable by the investigator in case of emergency or not capable to call the investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary goal of the trial is to show that treatment with plasma exchange plus therapeutic albumin replacement in patients with AMN induces a decrease of plasma and cerebrospinal fluid VLCFA.;Secondary Objective: The secondary goal of the trial is the assessment of efficacy and safety of the proposed treatment in 5 patients with AMN. Efficacy will be measured in terms of motor function and quality of life. Only in case of a decrease in VLCFA other biological markers (oxidation and inflammation biomarkers) will also be studied. Safety will be evaluated by clinical and biochemical exams and recording of any adverse event.;Primary end point(s): The main efficacy evaluation criterion is changes in plasma VLCFA between M0 and M6. C26:0, C24:0 and C26:0/C22:0 will be measured in plasma.;Timepoint(s) of evaluation of this end point: The assessment of the main variable is in month 6. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoints: 1) Tests evaluating the motor functions of treated AMN patients. They include: the Timed Up and Go (TUG) test, the Time to walk 25 feet (TW25), the 2 minute walk test (2MWT) and the 6 minute walk test (6MWT) on M0, M6 and M12. 2) Quality of life: score of SF-Qualiveen on M0, M6 and M12. 3) VLCFA in CSF (optional): C26:0, C24:0 and C26:0/C22:0 will be measured in CSF in those patients with AMN who voluntarily accept to undergo a lumbar puncture on M0, M6 and M12. 4) Biological measures (only in case of a decrease in VLCFA): - Marker of oxidative stress: 8oxo-dG in urine. 8oxo-dG will be measured on M0, M6 and M12. - Markers of inflammation: CCR3, CXCL5, CXCL9, IL9R, PPARd, GPX4 and STAT1 in RNA obtained from MNC and HGF, IL6, IL8, MCP-1, NGF, TNF and adiponectin in plasma will be measured on M0, M6 and M12. Safety endpoints: Safety will be evaluated by clinical and biochemical exams and recording of any adverse event.;Timepoint(s) of evaluation of this end point: The assessment of the secondary endpoints are in month 0, 6 i 12 (M0, M6, M12) | — |
Countries
Spain
Contacts
Public ContactAurora Pujol Onofre
Idibell (Institut d'Investigació Biomèdica de Bellvitge)
Outcome results
None listed