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

Phase 2 Selection Trial of High Dosage Creatine and Two Dosages of Tamoxifen in Amyotrophic Lateral Sclerosis (ALS)

Sponsors

Lead Sponsor: Nazem Atassi

Collaborator: ALS Therapy Alliance
State University of New York - Upstate Medical University

Source Massachusetts General Hospital
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).

Overall Status Completed
Start Date March 2011
Completion Date February 2013
Primary Completion Date December 2012
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Change in ALS Functional Rating Scale - Revised (ALSFRS-R) 38 weeks of treatment followed by a telephone interview at 42 weeks.
Secondary Outcome
Measure Time Frame
Vital Capacity/Pulmonary Function Testing 38 weeks of treatment followed by a telephone interview at 42 weeks.
Tracheostomy-free Survival 38 weeks of treatment followed by a telephone interview at 42 weeks.
Dose Adjustments 38 weeks of treatment followed by a telephone interview at 42 weeks.
Lab Abnormal Reports by Treatment Assignment 38 weeks of treatment followed by a telephone interview at 42 weeks.
Hand Held Dynamometry (HHD) Lower Z-score 38 weeks of treatment followed by a telephone interview at 42 weeks.
HHD Lower % Baseline 38 weeks of treatment followed by a telephone interview at 42 weeks.
HHD Upper Z-score 38 weeks of treatment followed by a telephone interview at 42 weeks.
HHD Upper % Baseline 38 weeks of treatment followed by a telephone interview at 42 weeks.
Accurate Test of Limb Isometric Strength (ATLIS) Lower Percentage of Predicted Normal (PPN) 38 weeks of treatment followed by a telephone interview at 42 weeks.
ATLIS Upper Percentage of Predicted Normal (PPN) 38 weeks of treatment followed by a telephone interview at 42 weeks.
Enrollment 60
Condition
Intervention

Intervention Type: Drug

Intervention Name: creatine

Description: creatine monohydrate powder

Arm Group Label: Creatine 30gm

Intervention Type: Drug

Intervention Name: tamoxifen

Description: Tamoxifen citrate capsules

Other Name: Nolvadex, Istubal, Valodex

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Nazem Atassi, MD, MMSc Principal Investigator Masaschusetts General Hospital, Boston, MA
Location
Facility:
University of Kansas Medical Center | Kansas City, Kansas, 66160, United States
Massachusetts General Hospital | Boston, Massachusetts, 02114, United States
University of Massachusetts Medical Center | Worcester, Massachusetts, 01655, United States
Washington University at St. Louis | St. Louis, Missouri, 63110, United States
SUNY Upstate Medical University | Syracuse, New York, 13210, United States
Carolinas Medical Center | Charlotte, North Carolina, 28203, United States
Pennsylvania State University, Hershey Medical Center | Hershey, Pennsylvania, 17033, United States
University of Washington Medical Center | Seattle, Washington, 98195, United States
Medical College of Wisconsin | Milwaukee, Wisconsin, 53226, United States
Location Countries

United States

Verification Date

December 2014

Responsible Party

Type: Sponsor-Investigator

Investigator Affiliation: Massachusetts General Hospital

Investigator Full Name: Nazem Atassi

Investigator Title: Nazem Atassi, MD. MMSc.

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Label: Creatine 30gm

Type: Experimental

Description: Creatine will be taken as a powder mixed into food or liquid twice a day. Volunteers in this arm will take a total of 30gm of creatine per day for 38 weeks. Volunteers will also take placebo capsules twice a day for 38 weeks. This is a blinded study, so neither participants nor study staff will know which treatment a volunteer is receiving. Creatine is a nutritional supplement and is not approved by the U.S. Food and Drug Administration (FDA) for treating ALS.

Label: Tamoxifen 40mg

Type: Experimental

Description: Tamoxifen will be taken as capsules twice a day. Volunteers in this arm will take a total of 40mg of tamoxifen per day for 38 weeks. Volunteers will also take placebo powder twice a day for 38 weeks. This is a blinded study, so neither participants nor study staff will know which treatment a volunteer is receiving. Tamoxifen is approved by the U.S. Food and Drug Administration (FDA) for breast cancer treatment but is not approved for treating ALS.

Label: Tamoxifen 80mg

Type: Experimental

Description: Tamoxifen will be taken as capsules twice a day. Volunteers in this arm will take a total of 80mg of tamoxifen per day for 38 weeks. Volunteers will also take placebo powder twice a day for 38 weeks. This is a blinded study, so neither participants nor study staff will know which treatment a volunteer is receiving. Tamoxifen is approved by the U.S. Food and Drug Administration (FDA) for breast cancer treatment but is not approved for treating ALS.

Acronym SDALS-001
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov