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

NCT01257581 | Completed Phase 2 Results DMC

• 1 other identifier: SDALS-001
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 9

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).

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS; Lou Gehrig's Disease; Amyotrophic Lateral Sclerosis; Creatine; Tamoxifen; Selection Design

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (10)

• 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.

Study Arms (3)

Creatine 30gm

EXPERIMENTAL

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.

Drug: creatine

Tamoxifen 40mg

EXPERIMENTAL

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.

Drug: tamoxifen

Tamoxifen 80mg

EXPERIMENTAL

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.

Drug: tamoxifen

Interventions

creatine DRUG

creatine monohydrate powder

Creatine 30gm

tamoxifen DRUG

Tamoxifen citrate capsules

Also known as: Nolvadex, Istubal, Valodex

Tamoxifen 40mg; Tamoxifen 80mg

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nazem Atassi: lead
• ALS Therapy Alliance: collaborator
• State University of New York - Upstate Medical University: collaborator

Study Sites (9)

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Massachusetts Medical Center

Worcester, Massachusetts, 01655, United States

Location

Washington University at St. Louis

St Louis, Missouri, 63110, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

Location

Pennsylvania State University, Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Links

• Northeast ALS Consortium website

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Creatine; Tamoxifen

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

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Nazem Atassi, MD
• Organization: Massachusetts General Hospital

natassi@partners.org

617-643-1807

Study Officials

• Nazem Atassi, MD, MMSc

  Masaschusetts General Hospital, Boston, MA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: SPONSOR INVESTIGATOR
• PI Title: Nazem Atassi, MD. MMSc.

Study Record Dates

• First Submitted: December 8, 2010
• First Posted: December 9, 2010
• Study Start: March 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: February 1, 2013
• Last Updated: December 4, 2014
• Results First Posted: December 4, 2014

Record last verified: 2014-12

Locations

US (9)