Plasma exchange by albumin replacement in Adrenomyeloneuropathy

Phase 1

• Conditions: Adrenomyeloneuropathy; MedDRA version: 20.0Level: LLTClassification code 10069075Term: Adrenomyeloneuropathy without cerebral involvementSystem Organ Class: 100000004850; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2019-004733-17-ES
• Lead Sponsor: Aurora Pujol Onofre

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-12-20
• Last Update Posted: 26 September 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 5

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

1. Any contraindication for plasma exchange due to behavioral disorders or abnormal coagulation parameters, such for example:
- Hypocalcemia (Ca++ < 8.7 mg/dl)
- Thrombocytopenia (< 100.000/µl)
- Fibrinogen < 1.5 g/l
- Prothrombin time (Quick) p< 60% versus control (INR > 1.5)
- Beta-blocker treatment and bradycardia < 55/min
- Treatment with ACIs (increased risk of allergic reactions)
2. Hemoglobin < 10 g/dl
3. Difficult venous access precluding plasma exchange
4. A history of frequent adverse reactions (serious or otherwise) to blood products
5. Hipersensibility to albumin o allergies to any of the components of Albunorm® 5%
6. Plasma creatine > 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.