Efficacy and Safety of Plasma Exchange With Albumin in Patients With Amyotrophic Lateral Sclerosis

Study Overview
=================
Brief Summary
-----------------
Pilot, phase II, prospective, open-label, uncontrolled study of plasma exchange with 5% albumin in 10 subjects having a definite, possible, or probable diagnosis of Amyotrophic Lateral Sclerosis (ALS).

Official Title
-----------------
Pilot Study on the Effects of Plasma Exchange on Motor Dysfunction and Cognitive Function in Patients With Amyotrophic Lateral Sclerosis

Conditions
-----------------
Amyotrophic Lateral Sclerosis

Intervention / Treatment
-----------------
* Biological: Albumin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed written-informed consent. Subjects over 18 years of age, and less than 70 years old. Subjects with a definite, possible, or probable diagnosis of ALS, according to the revised El Escorial criteria. Subjects having experienced their first ALS symptoms within 18 months before recruitment/consent. FVC > 70% Subjects must be medically suitable for study participation and of complying with all planned aspects of the protocol including blood sampling at the time of inclusion in the study. Exclusion Criteria: 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 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 anticoagulants 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.)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Albumin<br>Plasma exchange with Albumin | Biological: Albumin<br>* 27 plasma exchange procedures using Albumin 5% (estimated 3000 mL per plasma exchange) as replacement solution: three weeks of intensive treatment with two plasma exchanges per week twenty-one weeks of maintenance treatment with one weekly plasma exchange<br>* Other names: Albutein 5%;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) | Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) includes 12 questions classified into 3 subdomains: bulbar function (3 questions), fine and gross motor skills (6 questions), and respiratory function (3 questions) to assess the level self sufficiency. Each task was graded according to a 5-point scale from 0 (incapable) to 4 (normal ability) with a total score from 0 (worst) to 48 (best). | Baseline, Weeks 4, 12, 25, 36, and 48 | 
| Changes From Baseline in Percent Predicted Forced Vital Capacity (FVC) |  | Baseline, Weeks 4, 12, 25, 36, and 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes From Baseline in ALS Cognitive Function Determined by the ALS-Cognitive Behavioral Screen (ALS-CBS) Test | ALS-CBS test is composed of 2 sections. The first section of the ALS-CBS test includes a questionnaire completed by the caregiver regarding behavior and symptoms status. It is comprised of 15 questions inquiring about possible changes over time in participant's behavior that the caregiver has noticed since the onset of ALS symptoms. Each item is scored on a scale ranging from 0 (worst) to 3 (best) yielding a total 0= large changes to 45=no changes. There were 4 additional questions related to current behavioral symptoms (depression, anxiety, fatigue, and emotional liability). Each question was scored as 0= the presence of symptoms and 1= no current symptoms, giving a total score between 0 and 4. The second section of the ALB-CBS test is for cognitive screening and consists of four items: attention, concentration, follow-up and monitoring, and initiation and recovery. These items were scored 0-5 with a maximum score of 20 (0= cognitive impairment, 20= no apparent cognitive impairment). | Baseline, Weeks 25 and 48 | 
| Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Surface electromyography was performed to record motor evoked potential in the distal muscles of the upper limbs (thenar and hypothenar eminence) and dorsiflexor muscles of the lower limbs (anterior tibialis) after electrical stimulation. | Baseline, Weeks 4, 12, 25, 36, and 48 | 
| Changes From Baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40). | The Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-40) consists of 40 items grouped into 5 representative dimensions associated with quality of life. The first 4 scales (physical mobility, activities of daily living, food and drink, communication) refer to deficits and subsequent disabilities as a result of the disease. The fifth scale (emotional functioning) reflects how the subject is facing his/her physical deterioration emotionally. Each item is scored from 0 to 4 according to a gradation of symptom onset frequency (never, rarely, sometimes, often, and always). From raw scores, an index from 0 to 100 is obtained for each dimension, which allow comparisons to be made with the other dimensions as well as a straightforward interpretation of results (0 = better state of health as measured by the questionnaire; 100 = poorer state of health). | Baseline, Weeks 25 and 48 | 
| Percentage of Plasma Exchange Sessions Associated With One Adverse Event or Adverse Reaction, Including Clinically Significant Changes in Vital Signs or Lab Parameters |  | During the Treatment Phase (24 weeks) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
plasma exchange, albumin