Pilot study to evaluate the effect of plasma exchange with albumin in patients with amyotrophic lateral sclerosis

• Register: EUCTR
• Last refreshed on: 4 July 2016
• Main ID: EUCTR2013-004842-40-ES
• Date of registration: 07/03/2014
• Prospective Registration: Yes
• Primary sponsor: Instituto Grifols S.A.
• Public title: Pilot study to evaluate the effect of plasma exchange with albumin in patients with amyotrophic lateral sclerosis
• Scientific title: Pilot study to evaluate the effect of plasma exchange in motor and cognitive function in patients with amyotrophic lateral sclerosis - Albumin in ALS
• Date of first enrolment: 09/05/2014
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004842-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Spain

Contacts

• Name: Miquel Barceló
• Affiliation: Instituto Grifols S.A.

• Name: Miquel Barceló
• Affiliation: Instituto Grifols S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
In order to be eligible for participation in the trial, the patients must meet the following requirements:
- Must give written informed consent.
- Age ?18 and <70 years.
- Subjects with diagnosis of definitive, posible and probable ALS according El Escorial-Arlie criteria.
- Subjects with ALS symptom onset < 18 months from recruitment.
- FVC > 70%.
- Be medically able to undergo study procedures and to comply with the visits schedule at the time of inclusion in the study.
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 10
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients meeting any of the following criteria will not be able to participate in the trial:
- Subjects with a clinically significant preexisting lung disease not attributable to ALS.
- Subjects with a diagnosis of other neurodegenerative diseases or diseases associated with dysfunction of the motor neurons that can confuse the diagnosis of ALS.
- Participation in other clinical trials, or the reception of any other investigational drug in the six months prior to the start of the study.
- Female subjects who are pregnant, currently breastfeeding, or attempting to conceive during the study.
- Difficult peripheral venous access precluding plasma exchange and inability to implement a viable alternative catheter to make continued performing plasma exchange visits according to protocol
- Any contraindication for plasma exchange or abnormal coagulation parameters according clinical criteria from apheresis team (Banc de Sang i Teixits, BST Bellvitge).
- A history of frequent adverse reactions (serious or otherwise) to blood products.
- Hypersensitivity to albumin or allergies to any of the components of Albutein®.
- Subjects that can not interrupt treatment with acetylsalicylic acid or oral anticoaguants
- Plasma creatinine > 2mg/dl.
- Present a history of heart disease including ischemic heart disease or congestive heart failure.
- Presence of prior conduct disorders requiring pharmacologic intervention, with less than 3 months of stable treatment
- Any condition that complicates adherence to study protocol (illness with less than one year of expected survival , drug or alcohol abuse, etc.)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Amytrophic Lateral Sclerosis (ALS)
MedDRA version: 16.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: Albutein 5%
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: albúmina humana
Other descriptive name: HUMAN ALBUMIN SOLUTION
Concentration unit: g/l gram(s)/litre
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Secondary Objective: Evaluate the effect of plasma exchange in ALS-related:
- Cognitive dysfunction
- Systemic inflammatory response
- Oxidative Stress
- Non-directed metabolome profile
- Safety and tolerability

Timepoint(s) of evaluation of this end point: ALSFRS-R (6 measurements: week 0, 4, 12, 25, 36 y 48).
FVC (6 measurements: week 0, 4, 12, 25 36 y 48).

Primary end point(s): Change from baseline in the functional scale ALSFRS-R (ALS functional rating scale-revised)
Change from baseline in Forced Vital Capacity (FVC)

Main Objective: Evaluate the progress of the disease through functional scale (ALSFRS-R) and forced vital capacity (FVC) of patients with ALS treated with plasma exchange.

Secondary Outcome(s)

Secondary end point(s): Secondary endpoints :
- Changes from baseline in cognitive function as determined by clinical judgment, ALS -CBS test and Neary criteria for Frontotemporal Dementia (FTD)
- Assessment electromyography muscle strength through evoked motor potential from tena, hypothenar and anterior tibial muscles
- Assessment of quality of life through ALSA Q40 test.
- Change in non-directed metabolome profile in cerebrospinal fluid (CSF ) and in plasma
- Changes in plasma of albumin functional capacity
- Changes in plasma of oxidative stress parameters
- Changes in plasma of inflammatory mediators
- Variations in CSF of oxidative stress parameters and inflammatory mediators

Safety Variables :
- The primary criterion of safety will be the percentage of plasma exchanges associated with at least one adverse event that may be related to the study procedure (adverse reactions) within 72h after the infusion completion.
- In addition, the percentage of plasma exchanges involving some adverse event whether or not related to the procedure, will be considered in general
- Vital signs will be recorded before, during and after each plasma exchange session, where required. Various laboratory test parameters (blood cell counts, platelet count, prothrombin time (Quick), aPTT, fibrinogen, total proteins, and calcium) will be also assessed when necessary.
- According to the criterion of the investigator, all clinically relevant changes in vital function, laboratory test parameters will be evaluated.

Timepoint(s) of evaluation of this end point: - ALS -CBS test and Neary criteria (3 measurements week 0, 25 and 36)
- Electromyography muscle strength (6 measurements week 0, 4, 12, 25, 36 and 48).
- ALSA Q40 test (3 measurements week 0, 25 and 48)
- Non-directed metabolome profile in CSF and in plasma (3 measurements week 0, 12 and 25)
- Albumin functional capacity (6 measurements week 0, 4, 12, 25, 36 and 48)
- Oxidative stress parameters and inflammatory mediators in plasma (6 measurements week 0, 4, 12, 25, 36 and 48)
- Oxidative stress parameters and inflammatory mediators in CSF (3 measurements week 0, 12 and 25)

Secondary ID(s)

IG1309

Source(s) of Monetary Support

Instituto Grifols S.A.