Amyotrophic Lateral Sclerosis
Conditions
Keywords
plasma exchange, albumin
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).
Interventions
BIOLOGICALAlbumin
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
Sponsors
Instituto Grifols, S.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Albumin Plasma exchange with Albumin
Albumin: 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 | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Albumin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 48.9 years STANDARD_DEVIATION 9.86 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment Spain | 13 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 13 |
| other Total, other adverse events | 12 / 13 |
| serious Total, serious adverse events | 4 / 13 |
Outcome results
Primary
Changes From Baseline in Percent Predicted Forced Vital Capacity (FVC)
Time frame: Baseline, Weeks 4, 12, 25, 36, and 48
Population: Two subjects discontinued from the study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Albumin | Changes From Baseline in Percent Predicted Forced Vital Capacity (FVC) | Week 12 | -3.5 percentage of predicted value |
| Albumin | Changes From Baseline in Percent Predicted Forced Vital Capacity (FVC) | Week 4 | -6.0 percentage of predicted value |
| Albumin | Changes From Baseline in Percent Predicted Forced Vital Capacity (FVC) | Week 25 | -9.0 percentage of predicted value |
| Albumin | Changes From Baseline in Percent Predicted Forced Vital Capacity (FVC) | Week 36 | -12.0 percentage of predicted value |
| Albumin | Changes From Baseline in Percent Predicted Forced Vital Capacity (FVC) | Week 48 | -23.0 percentage of predicted value |
Comparison: Change from Baseline at Week 48.p-value: 0.0006t-test, 1 sided
Primary
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).
Time frame: Baseline, Weeks 4, 12, 25, 36, and 48
Population: Two subjects discontinued from the study early.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Albumin | Changes From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) | Week 4 | -1.0 units on a scale |
| Albumin | Changes From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) | Week 12 | -1.5 units on a scale |
| Albumin | Changes From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) | Week 25 | -4.0 units on a scale |
| Albumin | Changes From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) | Week 36 | -5.5 units on a scale |
| Albumin | Changes From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) | Week 48 | -10.0 units on a scale |
Comparison: Change from Baseline at Week 48.p-value: <0.0001t-test, 1 sided
Secondary
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).
Time frame: Baseline, Weeks 25 and 48
Population: Two subjects discontinued from the study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Albumin | Changes From Baseline in ALS Cognitive Function Determined by the ALS-Cognitive Behavioral Screen (ALS-CBS) Test | Behavior Status Week 25 | 0.0 units on a scale |
| Albumin | Changes From Baseline in ALS Cognitive Function Determined by the ALS-Cognitive Behavioral Screen (ALS-CBS) Test | Behavior Status Week 48 | -1.0 units on a scale |
| Albumin | Changes From Baseline in ALS Cognitive Function Determined by the ALS-Cognitive Behavioral Screen (ALS-CBS) Test | Symptom Status Week 25 | 0.0 units on a scale |
| Albumin | Changes From Baseline in ALS Cognitive Function Determined by the ALS-Cognitive Behavioral Screen (ALS-CBS) Test | Symptom Status Week 48 | 0.0 units on a scale |
| Albumin | Changes From Baseline in ALS Cognitive Function Determined by the ALS-Cognitive Behavioral Screen (ALS-CBS) Test | Cognitive Screening Week 25 | 0.0 units on a scale |
| Albumin | Changes From Baseline in ALS Cognitive Function Determined by the ALS-Cognitive Behavioral Screen (ALS-CBS) Test | Cognitive Screening Week 48 | -1.0 units on a scale |
Secondary
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).
Time frame: Baseline, Weeks 25 and 48
Population: Two subject discontinued from the study early.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Albumin | Changes From Baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40). | Physical Mobility Week 25 | 10.0 units on a scale |
| Albumin | Changes From Baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40). | Physical Mobility Week 48 | 32.5 units on a scale |
| Albumin | Changes From Baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40). | ADL/Independence Week 25 | 12.5 units on a scale |
| Albumin | Changes From Baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40). | ADL/Independence Week 48 | 25.0 units on a scale |
| Albumin | Changes From Baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40). | Eating and Drinking Week 25 | 0.0 units on a scale |
| Albumin | Changes From Baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40). | Eating and Drinking Week 48 | 8.3 units on a scale |
| Albumin | Changes From Baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40). | Communication Week 25 | 0.0 units on a scale |
| Albumin | Changes From Baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40). | Communication Week 48 | 0.0 units on a scale |
| Albumin | Changes From Baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40). | Emotional Functioning Week 25 | 5.0 units on a scale |
| Albumin | Changes From Baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40). | Emotional Functioning Week 48 | 7.5 units on a scale |
Secondary
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.
Time frame: Baseline, Weeks 4, 12, 25, 36, and 48
Population: Two subjects were discontinued from the study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Right Hypothenar Eminence (ADM) Week 36 | 5.0 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Right Tibialis Anterior Week 0 | 2.6 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Right Tibialis Anterior Week 4 | 4.9 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Right Tibialis Anterior Week 12 | 3.1 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Right Tibialis Anterior Week 25 | 1.9 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Right Tibialis Anterior Week 36 | 2.1 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Right Tibialis Anterior Week 48 | 1.2 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Left Tibialis Anterior Week 0 | 3.2 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Left Tibialis Anterior Week 4 | 3.1 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Left Tibialis Anterior Week 12 | 3.3 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Left Tibialis Anterior Week 25 | 2.6 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Left Tibialis Anterior Week 36 | 2.1 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Left Tibialis Anterior Week 48 | 1.0 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Right Thenar Eminence (APB) Week 0 | 4.0 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Right Thenar Eminence (APB) Week 4 | 4.4 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Right Thenar Eminence (APB) Week 12 | 3.0 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Right Thenar Eminence (APB) Week 25 | 2.6 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Right Thenar Eminence (APB) Week 36 | 1.2 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Right Thenar Eminence (APB) Week 48 | 0.6 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Left Thenar Eminence (APB) Week 0 | 6.4 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Left Thenar Eminence (APB) Week 4 | 2.6 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Left Thenar Eminence (APB) Week 12 | 3.1 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Left Thenar Eminence (APB) Week 25 | 1.9 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Left Thenar Eminence (APB) Week 36 | 0.6 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Left Thenar Eminence (APB) Week 48 | 0.5 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Right Hypothenar Eminence (ADM) Week 0 | 6.4 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Right Hypothenar Eminence (ADM) Week 4 | 7.4 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Right Hypothenar Eminence (ADM) Week 12 | 5.8 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Right Hypothenar Eminence (ADM) Week 25 | 5.1 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Right Hypothenar Eminence (ADM) Week 48 | 3.2 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Left Hypothenar Eminence (ADM) Week 0 | 6.2 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Left Hypothenar Eminence (ADM) Week 4 | 5.5 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Left Hypothenar Eminence (ADM) Week 12 | 4.4 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Left Hypothenar Eminence (ADM) Week 25 | 3.8 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Left Hypothenar Eminence (ADM) Week 36 | 4.0 mV |
| Albumin | Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle | Left Hypothenar Eminence (ADM) Week 48 | 2.4 mV |
Secondary
Percentage of Plasma Exchange Sessions Associated With One Adverse Event or Adverse Reaction, Including Clinically Significant Changes in Vital Signs or Lab Parameters
Time frame: During the Treatment Phase (24 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Albumin | Percentage of Plasma Exchange Sessions Associated With One Adverse Event or Adverse Reaction, Including Clinically Significant Changes in Vital Signs or Lab Parameters | 0.9 percentage of PE sessions | Standard Deviation 2.22 |