Safety and Efficacy Study of Creatine and Tamoxifen in Volunteers With Amyotrophic Lateral Sclerosis (ALS)

Nazem Atassi60 enrolled

Overview

The purpose of the study is to evaluate the safety and efficacy of high dose creatine and two dosages of tamoxifen treatment in amyotrophic lateral sclerosis (ALS).

Amyotrophic lateral sclerosis (ALS) is a rare, neurodegenerative disorder that results in progressive wasting and paralysis of voluntary muscles. It is known that nerve cells called motor neurons die in the brains and spinal cords of people with amyotrophic lateral sclerosis (ALS). However, the cause of this cell death is unknown. In this double blind, randomized, selection design trial, researchers will evaluate the safety and effectiveness of creatine and tamoxifen in volunteers with ALS. There are a large number of potential drugs that may improve the survival or slow down the disease progression in people with ALS. The current strategy is to test one drug at a time against placebo. "Selection Design" is a different type of study design. A Selection Design study uses multiple drugs to screen against each other and picks the winner to take to a larger study. This design can speed the search for effective drugs to treat ALS. In this Selection Design study, each volunteer will take one active study drug (creatine 30gm, tamoxifen 40mg, or tamoxifen 80mg) and one placebo. Approximately 60 eligible volunteers with ALS will be recruited from multiple centers in the US that belong to the Northeast ALS Consortium (NEALS). Volunteers will be randomly assigned equally to the three treatment arms: creatine 30gm/day, tamoxifen 40mg/day and tamoxifen 80mg/day. Volunteers will take study treatment for 38 weeks. After screening and randomization, volunteers will be followed at weeks 4, 10, 18, 28 and week 38. A final telephone interview will occur at week 42 (off study drug).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Amyotrophic Lateral Sclerosis

Interventions

creatineDRUG

creatine monohydrate powder

tamoxifenDRUG

Tamoxifen citrate capsules

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Familial or sporadic ALS. * Disease duration from diagnosis no greater than 36 months at Screening Visit. * Aged 18 years or older. * Capable of providing informed consent and complying with trial procedures. * Vital capacity (VC) equal to or more than 50% predicted normal value for gender, height and age at the Screening Visit. * Not taking, or on a stable dose of riluzole (50mg bid) for at least 30 days prior to the Screening Visit. * Women must not be able to become pregnant for the duration of the study (e.g., post menopausal for at least one year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. Women of childbearing potential must have a negative serum pregnancy test at the Screening Visit and be non-lactating. Exclusion Criteria: * History of known sensitivity or intolerability to creatine monohydrate or tamoxifen citrate or to any other related compound. * Prior exposure to creatine or tamoxifen within 30 days of the Screening Visit. * Exposure to any investigational agent within 30 days of the Screening Visit. * Use of coumarin anticoagulants (warfarin sodium), rifampin, aminoglutethimide, medroxyprogesterone, letrozole, or bromocriptine. * Presence of any of the following clinical conditions: Clinical evidence of unstable medical or psychiatric illness at the Screening Visit; Screening aspartate aminotransferase (AST) \> 3 times the upper limit of normal or serum creatinine \> 1.5 mg/dl (133 umol/L); Permanent assisted ventilation or mechanical ventilation; or Lactating or have a positive serum pregnancy test at the Screening Visit. * History of any of the following: blood clots including deep vein thrombosis, pulmonary embolism, and stroke, cataracts, renal problems, endometrial cancer, uterine sarcoma, or diabetes mellitus.

Locations (9)

University of Kansas Medical Center

Kansas City, Kansas, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Massachusetts Medical Center

Worcester, Massachusetts, United States

Outcomes

Primary Outcomes

Change in ALS Functional Rating Scale - Revised (ALSFRS-R)

Primary efficacy will be assessed by analyzing the mean rate of decline in the ALS Functional Rating Scale-Revised (ALSFRS-R) score over nine months. The ALSFRS-R is a quickly administered (5 min) ordinal rating scale used to determine a subject's assessment of their capability and independence in 12 functional activities. There are 12 questions, graded by the subject 0-4 (4 is normal). Score of 0 (worst) to 48 (best). Reflects speech and swallowing, fine motor skills, large motor skills, and breathing.

Time frame: 38 weeks of treatment followed by a telephone interview at 42 weeks.

Secondary Outcomes

Vital Capacity/Pulmonary Function Testing

Secondary efficacy will be assessed by analyzing the change in the Slow Vital Capacity score over nine months. Vital Capacity is the maximum amount of air a person can expel from the lungs after a maximum inhalation. A subject's VC depends on their age, sex and height. The value is recorded as a percentage of predicted normal.

Time frame: 38 weeks of treatment followed by a telephone interview at 42 weeks.

Tracheostomy-free Survival

Secondary efficacy will be assessed by analyzing rate of tracheostomy-free survival at nine months.

Time frame: 38 weeks of treatment followed by a telephone interview at 42 weeks.

Dose Adjustments

These events were due to a double-blinded study design.

Time frame: 38 weeks of treatment followed by a telephone interview at 42 weeks.

Lab Abnormal Reports by Treatment Assignment

The safety data is summarized according to treatment arm. Total number of Adverse Events (AEs), AEs that cause study drug withdrawal and abnormal laboratory tests are compared among treatment arms. A lab abnormality was a result that was out of range and considered clinically significant by the site investigator.

Data from ClinicalTrials.gov

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