Therapy in Amyotrophic Lateral Sclerosis (TAME)

NCT02118727 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: TAME-ALS FD003937-01FDA
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 13

Brief 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 and a prognostic marker in patients with ALS. Funding Source: FDA - Orphan Products Development (OPD)

Conditions

Amyotrophic Lateral Sclerosis; Frontal Temporal Dementia

Keywords

ALS; FTD; Tau; pNF-H/C3

Outcome Measures

Primary Outcomes (1)

• 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.

  During 36 weeks of therapy

Other Outcomes (2)

• Measuring the Levels of Tau, Phosphorylated Neurofilament Heavy Chain (pNFH) and the pNFH/C3 Ratio in Blood

  36 weeks of treatment

• Slowing of Behavioral Decline in Those With FTD Characteristics Based on the NPI-Q and the ALS-Cognitive Behavioral Screen (CBS)™

  36 weeks of treatment

Study Arms (2)

Memantine

ACTIVE COMPARATOR

Up to 20 mg memantine taken by mouth twice a day for 36 weeks

Drug: Memantine

Placebo

PLACEBO COMPARATOR

Up to 2 placebo tablets taken by mouth twice a day for 36 weeks

Drug: Placebo (for Memantine)

Interventions

Memantine DRUG

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.

Also known as: Namenda

Memantine

Placebo (for Memantine) DRUG

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.

Also known as: Sugar pill manufactured to mimic memantine 10 mg

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• If female, pregnant or breast-feeding; or, if of childbearing age, an unwillingness to use birth control.
• Unwillingness to provide consent
• 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

Sponsors & Collaborators

• University of Kansas Medical Center: lead
• University of Missouri-Columbia: collaborator

Study Sites (13)

Phoenix Neurological Associates

Phoenix, Arizona, 85018, United States

Location

UC Irvine

Irvine, California, 92868, United States

Location

University of Florida

Jacksonville, Florida, 32209, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Kansas School of Medicine - Wichita

Wichita, Kansas, 67214, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

University of Missouri

Columbia, Missouri, 65201, United States

Location

CoxHealth

Springfield, Missouri, 65802, United States

Location

Providence Health Sciences

Portland, Oregon, 97225, United States

Location

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Austin Neuromuscular Center

Austin, Texas, 78759, United States

Location

Nerve & Muscle Center of Texas

Houston, Texas, 77030, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Pick Disease of the Brain

Interventions

Memantine; Sugars

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Frontotemporal Dementia; Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Carbohydrates

Results Point of Contact

• Title: Richard Barohn, MD
• Organization: University of Missouri Health Care

rbarohn@health.missouri.edu

573-882-3693

Study Officials

• Richard J Barohn, MD

  University of Missouri Health Care

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Executive Vice Chancellor for Health Affairs

Study Record Dates

• First Submitted: April 15, 2014
• First Posted: April 21, 2014
• Study Start: November 7, 2018
• Primary Completion: July 22, 2021
• Study Completion: July 22, 2021
• Last Updated: November 29, 2022
• Results First Posted: November 29, 2022

Record last verified: 2022-11

Locations

US (13)