Plasma Exchange With Albumin in AMN Patients

September 21, 2022 updated by: Onofre, Aurora Pujol, M.D.

Effect of Plasma Exchange With Albumin in Patients With Adrenomyeloneuropathy: Unicentric, Single Arm, Proof of Concept Study.

Adrenoleukodystrophy (X-ALD) is the most common genetic disorder of the brain white matter with an incidence of 1:14,700 births. It is caused by mutations in the ABCD1 gene, which encodes a transporter of very long-chain fatty acids (VCLFA) into the peroxisome for degradation. As a consequence VLCFA accumulate in tissues and plasma being the pathognomonic biomarker for diagnosis. The excess of VLCFA produces mitochondrial ROS and oxidative damage, a major factor driving X-ALD pathogenesis. Other key dysregulated pathways are energy production, mitochondrial biogenesis and respiration, proteostasis, and ER stress. Current therapeutic options are unsatisfactory, restricted to bone marrow transplant and gene therapy, for which most patients do not qualify. The encouraging results of plasma exchange (PE) with albumin replacement for Alzheimer's Disease prompted us to start this study. Our rationale is the following: In plasma, VLCFA are transported by lipoproteins and albumin. Albumin is the major transporter of fatty acids (FA) to the brain. ABCD1 deficiency induces inflammation and increases blood-brain barrier leakage, which could facilitate increased permeability to albumin. We posit that replacement of albumin would lower VLCFA levels in plasma through peripheral sink mechanisms, diminishing the quantity of VLCFA reaching the brain, and would prevent lipid peroxidation. A pilot proof-of-concept study in 5 X-ALD patients will be carried out to replace endogenous albumin through PE applied, once a week the first month and monthly for 5 months. A 6 months follow-up after the end of the treatment will be carried out.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
5

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • Barcelona
      • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
        • Bellvitge University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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 the 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

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Patients
Patients before and after the treatment
Drug: Albumin solution
plasma exchange with albumin, one per week for one month, then one per month for 5 months
Other Names:
  • plasma exchange

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Concentration of very long chain fatty acids
Time Frame: Change from baseline at 6 months
Concentration of C26:0, C24:0 fatty acids and C26:0/C22:0 ratio in plasma
Change from baseline at 6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
2 Minute Walk Test
Time Frame: Months 0, 6 and 12
It measures the distance an individual is able to walk over a total of two minutes on a hard, flat surface
Months 0, 6 and 12
6 Minute Walk Test
Time Frame: Months 0, 6 and 12
It measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface
Months 0, 6 and 12
Timed Up and Go (TUG) test
Time Frame: Months 0, 6 and 12
It consists in standing up, walking 3 meters, turning around, walk back to the chair and sitting back down, at regular pace
Months 0, 6 and 12
Time to walk 25 Feet (TW25)
Time Frame: Months 0, 6 and 12
The patient should walk 7.62 meters (25 feet) as quickly, but safely, as possible without running
Months 0, 6 and 12
Expanded disability status scale (EDSS)
Time Frame: Months 0, 6 and 12
This scale measures motor function, ranging from 0 (normal neurological examination) to 10 (death)
Months 0, 6 and 12
Ashworth scale
Time Frame: Months 0, 6 and 12
The Modified Ashworth Scale measures spasticity in patients with lesions of the CNS or neurological disorders. It ranges from 0 (no increase in tone) to 4 (affected part(s) rigid in flexion or extension).
Months 0, 6 and 12
SF-Qualiveen (Short-form Qualiveen)
Time Frame: Months 0, 6 and 12
The Qualiveen is a specific patients' health-related quality of life developed to assess the impact of urinary disorders in patients with neurological conditions. Response options are framed as 5-point Likert-type scales, with 0 indicating no impact of urinary problems on health-related quality of life and 4 indicating a high adverse impact.
Months 0, 6 and 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Onofre, Aurora Pujol, M.D.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 9, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 24, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 13, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 6, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 11, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 22, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 21, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • XAMNPEAP2019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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