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Trial record 1 of 1 for:    NCT02118727
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Therapy in Amyotrophic Lateral Sclerosis (TAME) (TAME)

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ClinicalTrials.gov Identifier: NCT02118727
Recruitment Status : Recruiting
First Posted : April 21, 2014
Last Update Posted : December 5, 2019
Sponsor:
Information provided by (Responsible Party):
Richard Barohn, MD, University of Kansas Medical Center

Tracking Information
First Submitted Date  ICMJE April 15, 2014
First Posted Date  ICMJE April 21, 2014
Last Update Posted Date December 5, 2019
Actual Study Start Date  ICMJE November 7, 2018
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 16, 2014)
Disease progression as measured by the number of points lost on the ALS Functional Rating-Scale-Revised (ALSFRS-R) [ Time Frame: During 36 weeks of therapy ]
The primary outcome measure will be disease progression as measured by the number of points lost on the ALS 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. Disease progression in numerous ALS clinical trials has been measured using the ALSFRS-R which is a 12 question rating scale used to determine each participant's assessment of their capability and independence in daily activities. The ALSFRS-R can be administered with high inter-rater reliability and test-retest reliability in person or over the phone. The advantages of using such a measurement to determine disease progression are that the categories are relevant to ALS, it is a sensitive and reliable tool, and the rate of decline correlates strongly with survival
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 4, 2019)
Measuring the levels of Tau, pNFH and the pNFH/C3 ratio in blood [ Time Frame: 36 weeks of treatment ]
Preliminary data have demonstrated that there are elevated levels of tau and phosphorylated neurofilament heavy chain (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. Recently published data have also shown a high sensitivity and specificity for the ratio of pNFH/C3 in the CSF for diagnosing ALS. These combinations of biomarkers could be markers for axonal injury and neuronal cell death.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2014)
Measuring the levels of Tau, pNFH and the pNFH/C3 ratio in CSF and blood [ Time Frame: 36 weeks of treatment ]
Preliminary data have demonstrated that there are elevated levels of tau and phosphorylated neurofilament heavy chain (pNF-H) in the CSF of patients with ALS as compared to healthy controls suggesting that these proteins could also be used for measuring a patient's disease progression. Recently published data have also shown a high sensitivity and specificity for the ratio of pNFH/C3 in the CSF for diagnosing ALS. These combinations of biomarkers could be markers for axonal injury and neuronal cell death.
Current Other Pre-specified Outcome Measures
 (submitted: April 16, 2014)
Slowing of behavioral decline in those with FTD characteristics based on the NPI-Q and the ALS-CBS [ Time Frame: the course of 36 weeks of treatment ]
It is demonstrated that up to half of patients with ALS may develop cognitive impairment during the course of the disease and up to 40% of ALS patients develop FTD. The ALS Cognitive Behavioral Screen (ALS-CBS™) and the Neuropsychiatric Inventory Questionnaire (NPI-Q), are two neuropsychological batteries that are validated, brief practical measures that will be administered. Previous data has shown that memantine can slow the progression of behavioral and cognitive decline in other neurodegenerative diseases, such as Alzheimer's, Parkinson's and Lewy Body Disease, that there may be potential for a positive effect in patients with ALS. These scales should be great indicators of not only the diagnosis frototemporal dysfunction and even FTD, but also whether memantine can have any positive effect upon the progression of these changes.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Therapy in Amyotrophic Lateral Sclerosis (TAME)
Official Title  ICMJE Multi-centered Double Blind, Placebo Controlled Study Evaluating the Safety and Efficacy of Memantine at 20 mg BID in Patients With ALS
Brief Summary

The purpose of this study is to determine if memantine at 20 mg BID 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-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 BID 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 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 BID, 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Amyotrophic Lateral Sclerosis
  • Frontal Temporal Dementia
Intervention  ICMJE
  • Drug: Memantine
    All randomized patients will be instructed to take one tablet once a day for the first week from a blinded bottle that contains 10 mg tablets or matching placebo. At week two, patients will be instructed to take one tablet twice a day from the 10 mg bottle or matching placebo. At week three, patients will be instructed to take two tablets in the morning from the 10 mg bottle and one tablet from the 10 mg bottle or the matching placebo bottle in the evening. At week four patients will be instructed to take two pills twice a day from the 10 mg bottle or matching placebo.
    Other Name: Namenda
  • Drug: Placebo (for Memantine)
    All randomized patients will be instructed to take one tablet once a day for the first week from a blinded bottle that contains 10 mg tablets or matching placebo. At week two, patients will be instructed to take one tablet twice a day from the 10 mg bottle or matching placebo. At week three, patients will be instructed to take two tablets in the morning from the 10 mg bottle and one tablet from the 10 mg bottle or the matching placebo bottle in the evening. At week four patients will be instructed to take two pills twice a day from the 10 mg bottle or matching placebo.
    Other Name: Sugar Pill manufactured to mimic Memantine 20 mg
Study Arms  ICMJE
  • Active Comparator: Memantine
    20mg taken by mouth every day BID for 32 weeks
    Intervention: Drug: Memantine
  • Placebo Comparator: Placebo
    Placebo (for Memantine) taken by mouth everyday BID for 32 weeks
    Intervention: Drug: Placebo (for Memantine)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 16, 2014)
90
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2022
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age 18-85
  2. Male or Female
  3. Clinically definite, probable, probable lab-supported, or possible ALS by El Escorial criteria
  4. ALSFRS-R > 25
  5. Must be willing to undergo longitudinal blood draws for biomarker analysis
  6. Must have a caregiver
  7. Availability and willingness to complete the study
  8. Capable of providing informed consent and complying with trial procedures
  9. 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.

Exclusion Criteria:

  1. Patients with FVC ≤ 60%
  2. History of liver disease
  3. Severe renal failure
  4. History of intolerance to memantine
  5. Onset of weakness for greater than 3 years
  6. Any other co-morbid condition which would make completion of the trial unlikely
  7. If female, pregnant or breast-feeding; or, if of childbearing age, an unwillingness to use birth control.
  8. Taking any trial medications. Non-trial medications are not cause for exclusion.
  9. Unwillingness to provide consent
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Andrew Heim (913) 945-9926 aheim2@kumc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02118727
Other Study ID Numbers  ICMJE TAME-ALS FD003937-01
FDA ( Other Grant/Funding Number: R01FD003937 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Richard Barohn, MD, University of Kansas Medical Center
Study Sponsor  ICMJE University of Kansas Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Richard D Barohn, MD University of Kansas Medical Center
PRS Account University of Kansas Medical Center
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP