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

• Albumin (Biological), also known as Human Albumin 5%, Albutein 5%: 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

Primary outcomes

• Changes From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) [Baseline, Weeks 4, 12, 25, 36, and 48]: 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).
• Changes From Baseline in Percent Predicted Forced Vital Capacity (FVC) [Baseline, Weeks 4, 12, 25, 36, and 48]

Secondary outcomes

• Changes From Baseline in ALS Cognitive Function Determined by the ALS-Cognitive Behavioral Screen (ALS-CBS) Test [Baseline, Weeks 25 and 48]: 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).
• Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle [Baseline, Weeks 4, 12, 25, 36, and 48]: 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.
• Changes From Baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40). [Baseline, Weeks 25 and 48]: 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).
• 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)]

Sex: All, ages: 18 Years to 70 Years

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.)

Participant flow

Outcome results

• Changes From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) (Primary), Median, units on a scale: Albumin -1.0 (-1.0 to 0.0) (p <0.0001)
• Changes From Baseline in Percent Predicted Forced Vital Capacity (FVC) (Primary), Median, percentage of predicted value: Albumin -6.0 (-9.0 to 2.0) (p 0.0006)
• Changes From Baseline in ALS Cognitive Function Determined by the ALS-Cognitive Behavioral Screen (ALS-CBS) Test (Secondary), Median, units on a scale: Albumin 0.0 (-3.0 to 2.0)
• Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle (Secondary), Median, mV: Albumin 2.6 (0.5 to 6.2)
• Changes From Baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40). (Secondary), Median, units on a scale: Albumin 10.0 (0.0 to 20.0)
• Percentage of Plasma Exchange Sessions Associated With One Adverse Event or Adverse Reaction, Including Clinically Significant Changes in Vital Signs or Lab Parameters (Secondary), Mean, percentage of PE sessions: Albumin 0.9 +/- 2.22

Adverse events

Time frame: Adverse events were collected throughout the study (48 weeks).

Serious adverse events by term

Other adverse events by term

• Results publication: Povedano M, Paipa A, Barcelo M, Woodward MK, Ortega S, Dominguez R, Aragones ME, Horrillo R, Costa M, Paez A. Plasma exchange with albumin replacement and disease progression in amyotrophic lateral sclerosis: a pilot study. Neurol Sci. 2022 May;43(5):3211-3221. doi: 10.1007/s10072-021-05723-z. Epub 2021 Nov 18. PMID 34791571