Amyotrophic Lateral SclerosisPhase 2TAMENCT02118727
Therapy in Amyotrophic Lateral Sclerosis (TAME)
A Phase 2 study testing Memantine in people with Amyotrophic Lateral Sclerosis and Frontal Temporal Dementia, run by University of Kansas Medical Center at 13 sites in United States.
Trial summary
The purpose of this study is to determine if memantine at up to 20 mg twice a day when used in conjunction with riluzole, can slow down the disease progression of patients with ALS including potentially improving their neuropsychiatric changes, as well as determine if serum biomarkers can be used both as a diagnostic… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis, Frontal Temporal Dementia
- What is being tested?
- Memantine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 89 participants
- Where
- 13 sitesUnited States
- Study dates
- 7 Nov 2018to 22 Jul 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-85
- Male or Female
- Clinically definite, probable, probable lab-supported, or possible ALS by El Escorial criteria
- ALSFRS-R > 25
- Must be willing to undergo longitudinal blood draws for biomarker analysis
- Availability and willingness to complete the study
- Capable of providing informed consent and complying with trial procedures
- If patients are taking riluzole and/or Radicava, they must be a on a stable dose for at least thirty days prior to the baseline.
Who cannot join
- Patients with forced vital capacity (FVC) ≤ 60%
- History of liver disease
- Severe renal failure
- History of intolerance to memantine
- Onset of weakness for greater than 3 years
- Any other co-morbid condition which would make completion of the trial unlikely
Show all 30Show fewer
- If female, pregnant or breast-feeding; or, if of childbearing age, an unwillingness to use birth control.
- Taking any investigational medications. If the patient was previously on investigational medications, a 30-day washout period is required before the baseline visit. Non-trial medications are not cause for exclusion.
- Unwillingness to provide consent
- Remote Inclusion Criteria:
- Age 18-85
- Male or Female
- Clinically definite, probable, probable lab-supported, or possible ALS by El Escorial criteria
- ALSFRS-R > 25
- Must be willing to undergo longitudinal blood draws for biomarker analysis. This may be foregone during the screening visit
- Availability and willingness to complete the study
- Capable of providing informed consent and complying with trial procedures
- If patients are taking riluzole and/or Radicava, they must be a on a stable dose for at least thirty days prior to the baseline
- Documentation of not clinically significant liver enzymes within the previous 6 months
- Remote Exclusion Criteria:
- Patients with FVC ≤ 60%*
- History of liver disease
- Severe renal failure
- History of intolerance to memantine
- Onset of weakness for greater than 3 years
- Any other co-morbid condition which would make completion of the trial unlikely
- If female, pregnant or breast-feeding; or, if of childbearing age, an unwillingness to use birth control.
- Taking any investigational medications. If the patient was previously on investigational medications, a 30-day washout period is required before the baseline visit. Non-trial medications are not cause for exclusion.
- Unwillingness to provide consent
- Since FVC cannot be captured during a remote screening visit, and acceptable FVC performed within the previous 90 days is acceptable. If an FVC is not available within the previous 90 days, the subject may be enrolled if the local site PI believes the subject has no significant shortness of breath or respiratory issues.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Austin Neuromuscular Center
Austin, Texas, 78759
University of Missouri
Columbia, Missouri, 65201
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033
Nerve & Muscle Center of Texas
Houston, Texas, 77030
UC Irvine
Irvine, California, 92868
University of Florida
Jacksonville, Florida, 32209
University of Kansas Medical Center
Kansas City, Kansas, 66160
University of Kentucky
Lexington, Kentucky, 40536
Phoenix Neurological Associates
Phoenix, Arizona, 85018
Providence Health Sciences
Portland, Oregon, 97225
University of Washington
Seattle, Washington, 98195
CoxHealth
Springfield, Missouri, 65802
University of Kansas School of Medicine - Wichita
Wichita, Kansas, 67214
About this study
Official title: Phase 2B Study of Memantine for the Treatment of Amyotrophic Lateral Sclerosis
The purpose of this study is to determine if memantine at up to 20 mg twice a day when used in conjunction with riluzole, can slow down the disease progression of patients with ALS including potentially improving their neuropsychiatric changes, as well as determine if serum biomarkers can be used both as a diagnostic and a prognostic marker in patients with ALS.
Funding Source: FDA - Orphan Products Development (OPD)
Read the detailed description
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects 30,000 Americans each year. Of these 30,000 Americans, it has been suggested that up to 50% will experience cognitive and behavioral changes in the form of frontotemporal dysfunction and up to 40% will meet criteria for frontotemporal dementia (FTD). Riluzole the only FDA approved agent for ALS extends a patient's lifespan by 2-3 months, and there are no proven therapies for the cognitive changes associated with ALS. More effective therapy for this universally fatal disease is desperately needed.
Results from an open label pilot trial of 20 patients treated with memantine at 10 mg twice a day suggested that treatment with the combination of memantine and riluzole slowed ALS disease progression. This trial also showed that levels of specific protein biomarkers in the cerebrospinal fluid (CSF) at baseline correlated with the rate of disease progression. A concurrent phase II study performed by Dr. Carvalho, found no effect with similar dosing; however, the study was limited in terms of power. Comments on previous failed drug trials in ALS have raised the concern that many ALS trials study a potential therapeutic agent at only a single dose and thus may miss the potential efficacy of non FDA approved doses; therefore, this proposed study will test a higher dose of memantine, 20 mg twice a day, in a double blind, placebo controlled, randomized trial of 90 patients with ALS to determine if a therapy of memantine, especially in combination with riluzole, can slow disease progression compared to treatment with riluzole alone or no treatment. Participants who experience treatment related adverse events may undergo dose reduction or discontinuation. The primary outcome measure will be the rate of disease progression as measured by the ALS Functional Rating Scale- Revised (ALSFRS-R). In addition the investigators will examine the cognitive deficits seen in ALS patients measured by the ALS Cognitive Behavioral Screen (ALS-CBS) and the Neuropsychiatric Inventory Questionnaire (NPI-Q). Finally the investigators will examine specific validated protein serum biomarkers to determine if there is a correlation between the levels of these biomarkers and the rate of disease progression. In particular the investigators will measure the ratio of phosphorylated heavy neurofilament to Complement 3 to see if this ratio is predictive of disease progression and if the levels change during therapy with memantine.
This project will offer unique insights into this untreatable disease. If this study confirms earlier results and suggests that memantine, when used in conjunction with riluzole, significantly slows down the progression of the disease, as well as ameliorates cognitive deficits in patients with fronto-temporal dysfunction, it will set the groundwork for conducting a larger phase III trial.
- Being tested
- Memantine, Placebo (for Memantine)
- Keywords
- ALS, FTD, Tau, pNF-H/C3
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Pick Disease of the Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MemantineDrug
Also called Namenda
All randomized patients will be instructed to take one tablet once a day for the first two weeks from a blinded bottle that contains 10 mg tablets or matching placebo. At week three, patients will be instructed to take one tablet twice a day from the 10 mg bottle or matching placebo. At week five, patients will be instructed to take one tablet in the morning and two tablets in the evening from the 10 mg bottle or matching placebo. At week seven patients will be instructed to take two tablets twice a day from the 10 mg bottle or matching placebo.
Placebo (for Memantine)Drug
Also called Sugar pill manufactured to mimic memantine 10 mg
All randomized patients will be instructed to take one tablet once a day for the first two weeks from a blinded bottle that contains 10 mg tablets or matching placebo. At week three, patients will be instructed to take one tablet twice a day from the 10 mg bottle or matching placebo. At week five, patients will be instructed to take one tablet in the morning and two tablets in the evening from the 10 mg bottle or matching placebo. At week seven patients will be instructed to take two tablets twice a day from the 10 mg bottle or matching placebo.
| Study group | Role | What they receive |
|---|---|---|
| Memantine | Active comparator | Up to 20 mg memantine taken by mouth twice a day for 36 weeks Receives: Drug: Memantine |
| Placebo | Placebo comparator | Up to 2 placebo tablets taken by mouth twice a day for 36 weeks Receives: Drug: Placebo (for Memantine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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.
Measured: During 36 weeks of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2014 (estimated)
- Study start7 Nov 2018
- Primary completion22 Jul 2021
- Study completion22 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by University of Kansas Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 89 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Kansas Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Missouri-Columbia
- Responsible party
- Principal investigator, Richard J. Barohn, MD, University of Missouri-Columbia
- Investigators
- Richard J Barohn, MD, Principal investigator, University of Missouri Health Care
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02118727
- Sponsor's protocol ID
- TAME-ALS FD003937-01
- Other IDs
- FDA
- Acronym
- TAME
- Status last verified
- Nov 2022
- First submitted
- 15 Apr 2014
- Last updated
- 29 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2B Study of Memantine for the Treatment of Amyotrophic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT02118727
- Acronym / sponsor ID
- TAME / TAME-ALS FD003937-01
- Keywords
- ALS, FTD, Tau, pNF-H/C3
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 89 participants (actual)
- Lead sponsor
- University of Kansas Medical CenterUniversity, hospital or other
- Collaborators
- University of Missouri-Columbia
- Study start
- 7 Nov 2018 (actual)
- Primary completion
- 22 Jul 2021 (actual)
- Study completion
- 22 Jul 2021 (actual)
- First posted
- 21 Apr 2014 (estimated)
- Results
- Posted 29 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if memantine at up to 20 mg twice a day when used in conjunction with riluzole, can slow down the disease progression of patients with ALS including potentially improving their neuropsychiatric changes, as well as determine if serum biomarkers can be used both as a diagnostic and a prognostic marker in patients with ALS.
Funding Source: FDA - Orphan Products Development (OPD)
Detailed description
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects 30,000 Americans each year. Of these 30,000 Americans, it has been suggested that up to 50% will experience cognitive and behavioral changes in the form of frontotemporal dysfunction and up to 40% will meet criteria for frontotemporal dementia (FTD). Riluzole the only FDA approved agent for ALS extends a patient's lifespan by 2-3 months, and there are no proven therapies for the cognitive changes associated with ALS. More effective therapy for this universally fatal disease is desperately needed.
Results from an open label pilot trial of 20 patients treated with memantine at 10 mg twice a day suggested that treatment with the combination of memantine and riluzole slowed ALS disease progression. This trial also showed that levels of specific protein biomarkers in the cerebrospinal fluid (CSF) at baseline correlated with the rate of disease progression. A concurrent phase II study performed by Dr. Carvalho, found no effect with similar dosing; however, the study was limited in terms of power. Comments on previous failed drug trials in ALS have raised the concern that many ALS trials study a potential therapeutic agent at only a single dose and thus may miss the potential efficacy of non FDA approved doses; therefore, this proposed study will test a higher dose of memantine, 20 mg twice a day, in a double blind, placebo controlled, randomized trial of 90 patients with ALS to determine if a therapy of memantine, especially in combination with riluzole, can slow disease progression compared to treatment with riluzole alone or no treatment. Participants who experience treatment related adverse events may undergo dose reduction or discontinuation. The primary outcome measure will be the rate of disease progression as measured by the ALS Functional Rating Scale- Revised (ALSFRS-R). In addition the investigators will examine the cognitive deficits seen in ALS patients measured by the ALS Cognitive Behavioral Screen (ALS-CBS) and the Neuropsychiatric Inventory Questionnaire (NPI-Q). Finally the investigators will examine specific validated protein serum biomarkers to determine if there is a correlation between the levels of these biomarkers and the rate of disease progression. In particular the investigators will measure the ratio of phosphorylated heavy neurofilament to Complement 3 to see if this ratio is predictive of disease progression and if the levels change during therapy with memantine.
This project will offer unique insights into this untreatable disease. If this study confirms earlier results and suggests that memantine, when used in conjunction with riluzole, significantly slows down the progression of the disease, as well as ameliorates cognitive deficits in patients with fronto-temporal dysfunction, it will set the groundwork for conducting a larger phase III trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Memantine | Active comparator | Drug: MemantineUp to 20 mg memantine taken by mouth twice a day for 36 weeks |
| Placebo | Placebo comparator | Drug: Placebo (for Memantine)Up to 2 placebo tablets taken by mouth twice a day for 36 weeks |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18-85
- Male or Female
- Clinically definite, probable, probable lab-supported, or possible ALS by El Escorial criteria
- ALSFRS-R > 25
- Must be willing to undergo longitudinal blood draws for biomarker analysis
Key exclusion criteria (30 listed)
- Patients with forced vital capacity (FVC) ≤ 60%
- History of liver disease
- Severe renal failure
- History of intolerance to memantine
- Onset of weakness for greater than 3 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MemantineAlso: NamendaAll randomized patients will be instructed to take one tablet once a day for the first two weeks from a blinded bottle that contains 10 mg tablets or matching placebo. At week three, patients will be instructed to take one tablet twice a day from the 10 mg bottle or matching placebo. At week five, patients will be instructed to take one tablet in the morning and two tablets in the evening from the 10 mg bottle or matching placebo. At week seven patients will be instructed to take two tablets twice a day from the 10 mg bottle or matching placebo. | Drug | Memantine |
| Placebo (for Memantine)Also: Sugar pill manufactured to mimic memantine 10 mgAll randomized patients will be instructed to take one tablet once a day for the first two weeks from a blinded bottle that contains 10 mg tablets or matching placebo. At week three, patients will be instructed to take one tablet twice a day from the 10 mg bottle or matching placebo. At week five, patients will be instructed to take one tablet in the morning and two tablets in the evening from the 10 mg bottle or matching placebo. At week seven patients will be instructed to take two tablets twice a day from the 10 mg bottle or matching placebo. | Drug | Placebo |
Primary outcome
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.
Time frame: During 36 weeks of therapy
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard J Barohn, MD principal investigator
University of Missouri Health Care
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Memantine in people with Amyotrophic Lateral Sclerosis and Frontal Temporal Dementia, run by University of Kansas Medical Center at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: During 36 weeks of therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2022; AzTrials last refreshed its copy on 3 Nov 2026.