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

Amyotrophic Lateral Sclerosis Clinical Trial

— SDALS-001  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01257581
• Other study ID #: SDALS-001
• Status: Completed
• Phase: Phase 2
• First received: December 8, 2010
• Last updated: December 3, 2014
• Start date: March 2011
• Est. completion date: February 2013

Study information

• Verified date: December 2014
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: February 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• creatine
creatine monohydrate powder
• tamoxifen
Tamoxifen citrate capsules

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Pennsylvania State University, Hershey Medical Center	Hershey	Pennsylvania
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Washington Medical Center	Seattle	Washington
United States	Washington University at St. Louis	St. Louis	Missouri
United States	SUNY Upstate Medical University	Syracuse	New York
United States	University of Massachusetts Medical Center	Worcester	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Nazem Atassi	ALS Therapy Alliance, State University of New York - Upstate Medical University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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.	38 weeks of treatment followed by a telephone interview at 42 weeks.	No
Secondary	Tracheostomy-free Survival	Secondary efficacy will be assessed by analyzing rate of tracheostomy-free survival at nine months.	38 weeks of treatment followed by a telephone interview at 42 weeks.	No
Secondary	Dose Adjustments	These events were due to a double-blinded study design.	38 weeks of treatment followed by a telephone interview at 42 weeks.	Yes
Secondary	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.	38 weeks of treatment followed by a telephone interview at 42 weeks.	Yes
Secondary	Hand Held Dynamometry (HHD) Lower Z-score	The HHD lower z-scores are means of z-scores for right and left knee extension, knee flexion, hip flexion, and ankle dorsiflexion with z-scores calculated relative to the baseline mean and standard deviation strength of each muscle group across all participants.	38 weeks of treatment followed by a telephone interview at 42 weeks.	No
Secondary	HHD Lower % Baseline	HHD % baseline measures are mean percent change for right and left knee extension, knee flexion, hip flexion, and ankle dorsiflexion from each participant's baseline.	38 weeks of treatment followed by a telephone interview at 42 weeks.	No
Secondary	HHD Upper Z-score	The HHD upper z-scores are means of z-scores for right and left shoulder flexion, elbow extension, elbow flexion, write extension and first dorsal interosseous muscles with z-scores calculated relative to the baseline mean and standard deviation strength of each muscle group across all participants.	38 weeks of treatment followed by a telephone interview at 42 weeks.	No
Secondary	HHD Upper % Baseline	The HHD % baseline measures are mean percent change for shoulder flexion, elbow extension, elbow flexion, wrist extension, and first dorsal interosseous muscles from each participant's baseline.	38 weeks of treatment followed by a telephone interview at 42 weeks.	No
Secondary	Accurate Test of Limb Isometric Strength (ATLIS) Lower Percentage of Predicted Normal (PPN)	The ATLIS PPN measures are percentages of predicted normal strength based on age, gender, height, and weight using normative data.	38 weeks of treatment followed by a telephone interview at 42 weeks.	No
Secondary	ATLIS Upper Percentage of Predicted Normal (PPN)	The ATLIS PPN measures are percentages of predicted normal strength based on age, gender, height, and weight using normative data.	38 weeks of treatment followed by a telephone interview at 42 weeks.	No

External Links

•   Northeast ALS Consortium website