Trial Outcomes & Findings for Therapy in Amyotrophic Lateral Sclerosis (TAME) (NCT NCT02118727)

Last Updated: 2022-11-29

Results Overview

The primary outcome measure will be disease progression as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) during the 36 weeks of therapy. The patient's rate of progression on active therapy during the 36 week treatment arm will be compared to the rate of progression of the placebo arm. The ALSFRS-R is a 12 question rating scale used to determine each participant's assessment of their capability and independence in daily activities. Possible values are from 0 to 48; higher score means better outcome.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

89 participants

Primary outcome timeframe

During 36 weeks of therapy

Results posted on

2022-11-29

Participant Flow

Participant milestones

Participant milestones
Measure	Memantine Up to 20 mg memantine taken by mouth twice a day for 36 weeks.	Placebo Up to 2 placebo tablets taken by mouth twice a day for 36 weeks.
Overall Study STARTED	58	31
Overall Study COMPLETED	33	20
Overall Study NOT COMPLETED	25	11

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Baseline FVC values were collected for 44/58 participants randomized to memantine and 27/31 participants randomized to placebo.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Memantine n=58 Participants Up to 20 mg memantine taken by mouth twice a day for 36 weeks.	Placebo n=31 Participants Up to 2 placebo tablets taken by mouth twice a day for 36 weeks.	Total n=89 Participants Total of all reporting groups
Age, Continuous	62 years n=58 Participants	63 years n=31 Participants	63 years n=89 Participants
Sex: Female, Male Female	27 Participants n=58 Participants	10 Participants n=31 Participants	37 Participants n=89 Participants
Sex: Female, Male Male	31 Participants n=58 Participants	21 Participants n=31 Participants	52 Participants n=89 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=58 Participants	0 Participants n=31 Participants	0 Participants n=89 Participants
Race (NIH/OMB) Asian	3 Participants n=58 Participants	0 Participants n=31 Participants	3 Participants n=89 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=58 Participants	0 Participants n=31 Participants	0 Participants n=89 Participants
Race (NIH/OMB) Black or African American	1 Participants n=58 Participants	0 Participants n=31 Participants	1 Participants n=89 Participants
Race (NIH/OMB) White	53 Participants n=58 Participants	30 Participants n=31 Participants	83 Participants n=89 Participants
Race (NIH/OMB) More than one race	0 Participants n=58 Participants	0 Participants n=31 Participants	0 Participants n=89 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=58 Participants	1 Participants n=31 Participants	2 Participants n=89 Participants
Region of Enrollment United States	58 participants n=58 Participants	31 participants n=31 Participants	89 participants n=89 Participants
ALSFRS-R	36.33 units on a scale STANDARD_DEVIATION 5.50 • n=58 Participants	38.1 units on a scale STANDARD_DEVIATION 5.37 • n=31 Participants	36.94 units on a scale STANDARD_DEVIATION 5.49 • n=89 Participants
Forced vital capacity (FVC)	86.62 % of the predicted value STANDARD_DEVIATION 15.51 • n=44 Participants • Baseline FVC values were collected for 44/58 participants randomized to memantine and 27/31 participants randomized to placebo.	82.02 % of the predicted value STANDARD_DEVIATION 15.15 • n=27 Participants • Baseline FVC values were collected for 44/58 participants randomized to memantine and 27/31 participants randomized to placebo.	83.05 % of the predicted value STANDARD_DEVIATION 18.82 • n=71 Participants • Baseline FVC values were collected for 44/58 participants randomized to memantine and 27/31 participants randomized to placebo.
Symptom Duration	11.31 Months STANDARD_DEVIATION 5.44 • n=58 Participants	11.61 Months STANDARD_DEVIATION 6.44 • n=31 Participants	11.42 Months STANDARD_DEVIATION 5.77 • n=89 Participants

PRIMARY outcome

Timeframe: During 36 weeks of therapy

Population: Includes the 54/58 participants randomized to memantine and 29/31 participants randomized to placebo with more than one ALSFRS-R value.

Outcome measures

Outcome measures
Measure	Memantine n=54 Participants Up to 20 mg memantine taken by mouth twice a day for 36 weeks.	Placebo n=29 Participants Up to 2 placebo tablets taken by mouth twice a day for 36 weeks.
The Primary Comparison for Efficacy Will be Based on a Linear Mixed Effects (LME) Model Fit to the ALSFRS-R Data for the Patients Followed Over 36 Weeks.	-0.290 score on a scale/week Standard Error 0.39	-0.281 score on a scale/week Standard Error 0.32

OTHER_PRE_SPECIFIED outcome

Timeframe: 36 weeks of treatment

Preliminary data have demonstrated that there are elevated levels of Tau and pNF-H in the blood of patients with ALS as compared to healthy controls suggesting that these proteins could also be used for measuring a patient's disease progression.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 36 weeks of treatment

The ALS Cognitive Behavioral Screen (ALS-CBS™) and the Neuropsychiatric Inventory Questionnaire (NPI-Q), are two neuropsychological batteries that are validated measurements of frontotemporal dementia (FTD). The ALS-CBS questionnaire rates changes perceived in the patient by the caregiver. Possible values for the Cognitive score are from 0-20, and for the Behavior score are from 0-45. A higher score means better outcome. The NPI-Q provides an informant-based assessment of neuropsychiatric symptoms and associated caregiver distress for evaluating psychopathology in dementia. Possible values for the 12 item Total NPI score are from 0-36, and for the 12 item Total Distress score are from 0-30. A lower score means a better outcome

Outcome measures

Outcome data not reported

Adverse Events

Memantine

Serious events: 8 serious events

Other events: 46 other events

Deaths: 3 deaths

Placebo

Serious events: 3 serious events

Other events: 19 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Memantine n=58 participants at risk Up to 20 mg memantine taken by mouth twice a day for 36 weeks.	Placebo n=31 participants at risk Up to 2 placebo tablets taken by mouth twice a day for 36 weeks.
Infections and infestations Lung infection	5.2% 3/58 • Number of events 3 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.	0.00% 0/31 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.
General disorders Flu like symptoms	1.7% 1/58 • Number of events 1 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.	0.00% 0/31 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.7% 1/58 • Number of events 1 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.	0.00% 0/31 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.
Infections and infestations Catheter related infection	1.7% 1/58 • Number of events 1 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.	0.00% 0/31 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.
Gastrointestinal disorders Rectal hemorrhage	1.7% 1/58 • Number of events 1 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.	0.00% 0/31 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.
Gastrointestinal disorders Colitis	0.00% 0/58 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.	3.2% 1/31 • Number of events 1 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.
Vascular disorders Hematoma	0.00% 0/58 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.	3.2% 1/31 • Number of events 1 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/58 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.	3.2% 1/31 • Number of events 1 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.
Vascular disorders Thromboembolic event	0.00% 0/58 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.	3.2% 1/31 • Number of events 1 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.
Injury, poisoning and procedural complications Infusion related reaction	1.7% 1/58 • Number of events 1 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.	0.00% 0/31 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.
Infections and infestations Sepsis	1.7% 1/58 • Number of events 1 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.	0.00% 0/31 • 40 weeks Adverse Events - Clinical abnormalities that begin or worsen and are not thought to be directly related to the expected course of ALS itself, whether or not the abnormality is believed by the investigator to be related to the study medication. Serious Adverse Events - Life threatening, fatal, result in hospitalization or prolong hospitalization, permanent disability, congenital anomaly, cancer, or overdose, or are any event that the investigator believes is very unusual or potentially serious.

Other adverse events

Additional Information

Richard Barohn, MD

University of Missouri Health Care

Phone: 573-882-3693

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place