Amyotrophic Lateral SclerosisPhase 2SDALS-001NCT01257581
Safety and Efficacy Study of Creatine and Tamoxifen in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
A Phase 2 study testing creatine and tamoxifen in people with Amyotrophic Lateral Sclerosis, run by Nazem Atassi at 9 sites in United States.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- creatine and tamoxifen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 9 sitesUnited States
- Study dates
- Mar 2011to Feb 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Carolinas Medical Center
Charlotte, North Carolina, 28203
Pennsylvania State University, Hershey Medical Center
Hershey, Pennsylvania, 17033
University of Kansas Medical Center
Kansas City, Kansas, 66160
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
University of Washington Medical Center
Seattle, Washington, 98195
Washington University at St. Louis
St Louis, Missouri, 63110
SUNY Upstate Medical University
Syracuse, New York, 13210
University of Massachusetts Medical Center
Worcester, Massachusetts, 01655
About this study
Official title: Phase 2 Selection Trial of High Dosage Creatine and Two Dosages of Tamoxifen in Amyotrophic Lateral Sclerosis (ALS)
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).
Read the 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).
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- creatine, tamoxifen
- Keywords
- ALS, Lou Gehrig's Disease, Amyotrophic Lateral Sclerosis, Creatine, Tamoxifen, Selection Design
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
creatineDrug
creatine monohydrate powder
tamoxifenDrug
Also called Nolvadex, Istubal, Valodex
Tamoxifen citrate capsules
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: tamoxifen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 38 weeks of treatment followed by a telephone interview at 42 weeks.
Secondary outcomes (10)
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.
Measured: 38 weeks of treatment followed by a telephone interview at 42 weeks.
Tracheostomy-free Survival
Secondary efficacy will be assessed by analyzing rate of tracheostomy-free survival at nine months.
Measured: 38 weeks of treatment followed by a telephone interview at 42 weeks.
Dose Adjustments
These events were due to a double-blinded study design.
Measured: 38 weeks of treatment followed by a telephone interview at 42 weeks.
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.
Measured: 38 weeks of treatment followed by a telephone interview at 42 weeks.
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.
Measured: 38 weeks of treatment followed by a telephone interview at 42 weeks.
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.
Measured: 38 weeks of treatment followed by a telephone interview at 42 weeks.
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.
Measured: 38 weeks of treatment followed by a telephone interview at 42 weeks.
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.
Measured: 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)
The ATLIS PPN measures are percentages of predicted normal strength based on age, gender, height, and weight using normative data.
Measured: 38 weeks of treatment followed by a telephone interview at 42 weeks.
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.
Measured: 38 weeks of treatment followed by a telephone interview at 42 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2010 (estimated)
- Study startMar 2011
- Primary completionDec 2012
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nazem Atassi
- Sponsor type
- University, hospital or other
- Collaborators
- ALS Therapy Alliance, State University of New York - Upstate Medical University
- Responsible party
- Sponsor-investigator, Nazem Atassi, Massachusetts General Hospital
- Investigators
- Nazem Atassi, MD, MMSc, Principal investigator, Masaschusetts General Hospital, Boston, MA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01257581
- Sponsor's protocol ID
- SDALS-001
- Acronym
- SDALS-001
- Status last verified
- Dec 2014
- First submitted
- 8 Dec 2010
- Last updated
- 4 Dec 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Selection Trial of High Dosage Creatine and Two Dosages of Tamoxifen in Amyotrophic Lateral Sclerosis (ALS)
- ClinicalTrials.gov ID
- NCT01257581
- Acronym / sponsor ID
- SDALS-001 / SDALS-001
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- ALS, Lou Gehrig's Disease, Amyotrophic Lateral Sclerosis, Creatine, Tamoxifen, Selection Design
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Nazem AtassiUniversity, hospital or other
- Collaborators
- ALS Therapy Alliance, State University of New York - Upstate Medical University
- Study start
- Mar 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 9 Dec 2010 (estimated)
- Results
- Posted 4 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Creatine 30gm | Experimental | Drug: creatineCreatine 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 40mg | Experimental | Drug: tamoxifenTamoxifen 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 80mg | Experimental | Drug: tamoxifenTamoxifen 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| creatinecreatine monohydrate powder | Drug | Creatine 30gm |
| tamoxifenAlso: Nolvadex, Istubal, ValodexTamoxifen citrate capsules | Drug | Tamoxifen 40mg, Tamoxifen 80mg |
Primary outcome
Change in ALS Functional Rating Scale - Revised (ALSFRS-R)
Time frame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
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.
10 secondary outcomes
Vital Capacity/Pulmonary Function Testing
Time frame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
Tracheostomy-free Survival
Time frame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
Dose Adjustments
Time frame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
Lab Abnormal Reports by Treatment Assignment
Time frame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
Hand Held Dynamometry (HHD) Lower Z-score
Time frame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
HHD Lower % Baseline
Time frame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
HHD Upper Z-score
Time frame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
HHD Upper % Baseline
Time frame: 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)
Time frame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
ATLIS Upper Percentage of Predicted Normal (PPN)
Time frame: 38 weeks of treatment followed by a telephone interview at 42 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Northeast ALS Consortium websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nazem Atassi, MD, MMSc principal investigator
Masaschusetts General Hospital, Boston, MA
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing creatine and tamoxifen in people with Amyotrophic Lateral Sclerosis, run by Nazem Atassi at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in ALS Functional Rating Scale - Revised (ALSFRS-R) (time frame: 38 weeks of treatment followed by a telephone interview at 42 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2014.