Back to results

Plasma Exchange With Albumin in AMN Patients

Primary Purpose

Adrenomyeloneuropathy, Adrenoleukodystrophy

Status

Completed

Phase

Phase 2

Locations

Spain

Study Type

Interventional

Intervention

Albumin solution

About this trial

This is an interventional treatment trial for Adrenomyeloneuropathy focused on measuring plasma exchange, albumin, VLCFA

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

Men of 18 to 65 years old, inclusive
Elevated plasma VLCFA and gene mutation identified
Clinical signs of AMN with at least pyramidal signs in the lower limbs and difficulties to run
Presence of motor deficit according to the EDSS scale
Ability to perform the 2MWT
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:

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)
Hemoglobin < 10 g/dl
Difficult venous access precluding plasma exchange
A history of frequent adverse reactions (serious or otherwise) to blood products
Hipersensibility to albumin o allergies to any of the components of Albunorm® 5%
Plasma creatine > 2 mg/dl
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)
Liver cirrhosis or any liver problem with GPT > 2.5 x ULN, or bilirubin > 2 mg/dl
Heart diseases as evidenced by myocardial infarction, severe or unstable angina, or heart failure in the past 12 months
Gadolinium enhancement on T1 sequence of any abnormal hypersignal of white matter, including myelinated pyramidal tracts, visible at brain MRI on FLAIR sequences
Significant peripheral edema (2+ or more on the Assessment Chart for Pitting Edema) of the extremities of any etiology
Any evolutive malignancy during the last five years or any condition complicating adherence to the study protocol
Smokers (one pack/ day or more for at least 20 years), current or former
Any psychiatric disease
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
Patients being treated with anticoagulants or antiplatelet therapy
Not easily contactable by the investigator in case of emergency or not capable to call the investigator

Sites / Locations

Bellvitge University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Patients

Arm Description

Patients before and after the treatment

Outcomes

Primary Outcome Measures

Concentration of very long chain fatty acids

Concentration of C26:0, C24:0 fatty acids and C26:0/C22:0 ratio in plasma

Secondary Outcome Measures

2 Minute Walk Test

It measures the distance an individual is able to walk over a total of two minutes on a hard, flat surface

6 Minute Walk Test

It measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface

Timed Up and Go (TUG) test

It consists in standing up, walking 3 meters, turning around, walk back to the chair and sitting back down, at regular pace

Time to walk 25 Feet (TW25)

The patient should walk 7.62 meters (25 feet) as quickly, but safely, as possible without running

Expanded disability status scale (EDSS)

This scale measures motor function, ranging from 0 (normal neurological examination) to 10 (death)

Ashworth scale

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).

SF-Qualiveen (Short-form Qualiveen)

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.

Full Information

NCT ID

NCT04303416

First Posted

March 6, 2020

Last Updated

September 21, 2022

Sponsor

Onofre, Aurora Pujol, M.D.

1. Study Identification

Unique Protocol Identification Number

NCT04303416

Brief Title

Plasma Exchange With Albumin in AMN Patients

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Completed

Study Start Date

March 9, 2020 (Actual)

Primary Completion Date

February 24, 2021 (Actual)

Study Completion Date

September 13, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Onofre, Aurora Pujol, M.D.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Adrenomyeloneuropathy, Adrenoleukodystrophy

Keywords

plasma exchange, albumin, VLCFA

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Patients

Arm Type

Experimental

Arm Description

Patients before and after the treatment

Intervention Type

Drug

Intervention Name(s)

Albumin solution

Other Intervention Name(s)

plasma exchange

Intervention Description

plasma exchange with albumin, one per week for one month, then one per month for 5 months

Primary Outcome Measure Information:

Title

Concentration of very long chain fatty acids

Description

Concentration of C26:0, C24:0 fatty acids and C26:0/C22:0 ratio in plasma

Time Frame

Change from baseline at 6 months

Secondary Outcome Measure Information:

Title

2 Minute Walk Test

Description

It measures the distance an individual is able to walk over a total of two minutes on a hard, flat surface

Time Frame

Months 0, 6 and 12

Title

6 Minute Walk Test

Description

It measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface

Time Frame

Months 0, 6 and 12

Title

Timed Up and Go (TUG) test

Description

It consists in standing up, walking 3 meters, turning around, walk back to the chair and sitting back down, at regular pace

Time Frame

Months 0, 6 and 12

Title

Time to walk 25 Feet (TW25)

Description

The patient should walk 7.62 meters (25 feet) as quickly, but safely, as possible without running

Time Frame

Months 0, 6 and 12

Title

Expanded disability status scale (EDSS)

Description

This scale measures motor function, ranging from 0 (normal neurological examination) to 10 (death)

Time Frame

Months 0, 6 and 12

Title

Ashworth scale

Description

Time Frame

Months 0, 6 and 12

Title

SF-Qualiveen (Short-form Qualiveen)

Description

Time Frame

Months 0, 6 and 12

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Men of 18 to 65 years old, inclusive Elevated plasma VLCFA and gene mutation identified Clinical signs of AMN with at least pyramidal signs in the lower limbs and difficulties to run Presence of motor deficit according to the EDSS scale Ability to perform the 2MWT 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: 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) Hemoglobin < 10 g/dl Difficult venous access precluding plasma exchange A history of frequent adverse reactions (serious or otherwise) to blood products Hipersensibility to albumin o allergies to any of the components of Albunorm® 5% Plasma creatine > 2 mg/dl 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) Liver cirrhosis or any liver problem with GPT > 2.5 x ULN, or bilirubin > 2 mg/dl Heart diseases as evidenced by myocardial infarction, severe or unstable angina, or heart failure in the past 12 months Gadolinium enhancement on T1 sequence of any abnormal hypersignal of white matter, including myelinated pyramidal tracts, visible at brain MRI on FLAIR sequences Significant peripheral edema (2+ or more on the Assessment Chart for Pitting Edema) of the extremities of any etiology Any evolutive malignancy during the last five years or any condition complicating adherence to the study protocol Smokers (one pack/ day or more for at least 20 years), current or former Any psychiatric disease 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 Patients being treated with anticoagulants or antiplatelet therapy Not easily contactable by the investigator in case of emergency or not capable to call the investigator

Facility Information:

Facility Name

Bellvitge University Hospital

City

L'Hospitalet de Llobregat

State/Province

Barcelona

ZIP/Postal Code

08908

Country

Spain

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

Plasma Exchange With Albumin in AMN Patients

We'll reach out to this number within 24 hrs