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Safety and Efficacy Study of Creatine and Tamoxifen in Volunteers With Amyotrophic Lateral Sclerosis (ALS) (SDALS-001)

Primary Purpose

Amyotrophic Lateral Sclerosis

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

creatine

tamoxifen

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring ALS, Lou Gehrig's Disease, Amyotrophic Lateral Sclerosis, Creatine, Tamoxifen, Selection Design

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Creatine 30gm

Tamoxifen 40mg

Tamoxifen 80mg

Arm 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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Tracheostomy-free Survival

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

Dose Adjustments

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

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.

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT01257581

First Posted

December 8, 2010

Last Updated

December 3, 2014

Sponsor

Nazem Atassi

Collaborators

ALS Therapy Alliance, State University of New York - Upstate Medical University

1. Study Identification

Unique Protocol Identification Number

NCT01257581

Brief Title

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

Acronym

SDALS-001

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2014

Overall Recruitment Status

Completed

Study Start Date

March 2011 (undefined)

Primary Completion Date

December 2012 (Actual)

Study Completion Date

February 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Nazem Atassi

Collaborators

ALS Therapy Alliance, State University of New York - Upstate Medical University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyotrophic Lateral Sclerosis

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Creatine 30gm

Arm Type

Experimental

Arm Description

Arm Title

Tamoxifen 40mg

Arm Type

Experimental

Arm Description

Arm Title

Tamoxifen 80mg

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

creatine

Intervention Description

creatine monohydrate powder

Intervention Type

Drug

Intervention Name(s)

tamoxifen

Other Intervention Name(s)

Nolvadex, Istubal, Valodex

Intervention Description

Tamoxifen citrate capsules

Primary Outcome Measure Information:

Title

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

Description

Time Frame