Clinical trial NCT01257581: Safety and Efficacy Study of Creatine and Tamoxifen in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
Official title: Phase 2 Selection Trial of High Dosage Creatine and Two Dosages of Tamoxifen in Amyotrophic Lateral Sclerosis (ALS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Keywords: ALS
Lou Gehrig's Disease
Amyotrophic Lateral Sclerosis
Creatine
Tamoxifen
Selection Design
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: ALS Therapy Alliance
name: State University of New York - Upstate Medical University
First posted: 2010-12-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Change in ALS Functional Rating Scale - Revised (ALSFRS-R)
timeFrame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
Secondary outcomes:
measure: Vital Capacity/Pulmonary Function Testing
timeFrame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
measure: Tracheostomy-free Survival
timeFrame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
measure: Dose Adjustments
timeFrame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
measure: Lab Abnormal Reports by Treatment Assignment
timeFrame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
measure: Hand Held Dynamometry (HHD) Lower Z-score
timeFrame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
measure: HHD Lower % Baseline
timeFrame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
measure: HHD Upper Z-score
timeFrame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
measure: HHD Upper % Baseline
timeFrame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
measure: Accurate Test of Limb Isometric Strength (ATLIS) Lower Percentage of Predicted Normal (PPN)
timeFrame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
measure: ATLIS Upper Percentage of Predicted Normal (PPN)
timeFrame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical Center
state: Massachusetts
city: St. Louis
country: United States
facility: Washington University at St. Louis
state: Missouri
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Hershey
country: United States
facility: Pennsylvania State University, Hershey Medical Center
state: Pennsylvania
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Masaschusetts General Hospital, Boston, MA
name: Nazem Atassi, MD, MMSc
role: PRINCIPAL_INVESTIGATOR
References: