AdrenomyeloneuropathyPhase 2/3NCT04303416
Plasma Exchange With Albumin in AMN Patients
A Phase 2/3 study testing Albumin solution in people with Adrenomyeloneuropathy and Adrenoleukodystrophy, run by Pujol, Aurora, M.D. at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men only
- Conditions the study is for
- Adrenomyeloneuropathy, Adrenoleukodystrophy
- What is being tested?
- Albumin solution
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteSpain
- Study dates
- 9 Mar 2020to 13 Sep 2021
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Spain1 site
Bellvitge University Hospital
L'Hospitalet de Llobregat, Barcelona, 08908
About this study
Official title: 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.
- Conditions
- Adrenomyeloneuropathy, Adrenoleukodystrophy
- Being tested
- Albumin solution
- Keywords
- plasma exchange, albumin, VLCFA
- Medical subject headings
- Adrenoleukodystrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Albumin solutionDrug
Also called plasma exchange
plasma exchange with albumin, one per week for one month, then one per month for 5 months
| Study group | Role | What they receive |
|---|---|---|
| Patients | Experimental | Patients before and after the treatment Receives: Drug: Albumin solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of very long chain fatty acids
Concentration of C26:0, C24:0 fatty acids and C26:0/C22:0 ratio in plasma
Measured: Change from baseline at 6 months
Secondary outcomes (7)
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
Measured: Months 0, 6 and 12
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
Measured: Months 0, 6 and 12
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
Measured: Months 0, 6 and 12
Time to walk 25 Feet (TW25)
The patient should walk 7.62 meters (25 feet) as quickly, but safely, as possible without running
Measured: Months 0, 6 and 12
Expanded disability status scale (EDSS)
This scale measures motor function, ranging from 0 (normal neurological examination) to 10 (death)
Measured: Months 0, 6 and 12
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).
Measured: Months 0, 6 and 12
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.
Measured: Months 0, 6 and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2020
- Study start9 Mar 2020
- Primary completion24 Feb 2021
- Study completion13 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AdrenomyeloneuropathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pujol, Aurora, M.D.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04303416
- Sponsor's protocol ID
- XAMNPEAP2019
- Status last verified
- Sep 2022
- First submitted
- 6 Mar 2020
- Last updated
- 22 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Plasma Exchange With Albumin in Patients With Adrenomyeloneuropathy: Unicentric, Single Arm, Proof of Concept Study.
- ClinicalTrials.gov ID
- NCT04303416
- Acronym / sponsor ID
- XAMNPEAP2019
- Conditions
- Adrenomyeloneuropathy, Adrenoleukodystrophy
- Keywords
- plasma exchange, albumin, VLCFA
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Pujol, Aurora, M.D.
- Study start
- 9 Mar 2020 (actual)
- Primary completion
- 24 Feb 2021 (actual)
- Study completion
- 13 Sep 2021 (actual)
- First posted
- 11 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients | Experimental | Drug: Albumin solutionPatients before and after the treatment |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (23 listed)
- Any contraindication for plasma exchange due to behavioral disorders or abnormal coagulation parameters, such for example:
- 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%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Albumin solutionAlso: plasma exchangeplasma exchange with albumin, one per week for one month, then one per month for 5 months | Drug | Patients |
Primary outcome
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
7 secondary outcomes
2 Minute Walk Test
Time frame: Months 0, 6 and 12
6 Minute Walk Test
Time frame: Months 0, 6 and 12
Timed Up and Go (TUG) test
Time frame: Months 0, 6 and 12
Time to walk 25 Feet (TW25)
Time frame: Months 0, 6 and 12
Expanded disability status scale (EDSS)
Time frame: Months 0, 6 and 12
Ashworth scale
Time frame: Months 0, 6 and 12
SF-Qualiveen (Short-form Qualiveen)
Time frame: Months 0, 6 and 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Albumin solution in people with Adrenomyeloneuropathy and Adrenoleukodystrophy, run by Pujol, Aurora, M.D. at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concentration of very long chain fatty acids (time frame: Change from baseline at 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2022.