Trial Outcomes & Findings for Safety and Efficacy Study of Creatine and Tamoxifen in Volunteers With Amyotrophic Lateral Sclerosis (ALS) (NCT NCT01257581)
NCT ID: NCT01257581
Last Updated: 2014-12-04
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
60 participants
Primary outcome timeframe
38 weeks of treatment followed by a telephone interview at 42 weeks.
Results posted on
2014-12-04
Participant Flow
Participant milestones
| Measure |
Creatine 30gm
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.
creatine: creatine monohydrate powder
|
Tamoxifen 40mg
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: Tamoxifen citrate capsules
|
Tamoxifen 80mg
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.
tamoxifen: Tamoxifen citrate capsules
|
|---|---|---|---|
|
Overall Study
STARTED
|
22
|
21
|
17
|
|
Overall Study
COMPLETED
|
17
|
18
|
11
|
|
Overall Study
NOT COMPLETED
|
5
|
3
|
6
|
Reasons for withdrawal
| Measure |
Creatine 30gm
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.
creatine: creatine monohydrate powder
|
Tamoxifen 40mg
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: Tamoxifen citrate capsules
|
Tamoxifen 80mg
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.
tamoxifen: Tamoxifen citrate capsules
|
|---|---|---|---|
|
Overall Study
Early Termination
|
3
|
1
|
2
|
|
Overall Study
Death
|
2
|
2
|
4
|
Baseline Characteristics
Safety and Efficacy Study of Creatine and Tamoxifen in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
Baseline characteristics by cohort
| Measure |
Creatine 30gm
n=22 Participants
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.
|
Tamoxifen 40mg
n=21 Participants
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.
|
Tamoxifen 80mg
n=17 Participants
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.
|
Total
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
55.5 years
STANDARD_DEVIATION 11.4 • n=5 Participants
|
60.3 years
STANDARD_DEVIATION 10.6 • n=7 Participants
|
56.3 years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
57.4 years
STANDARD_DEVIATION 11.1 • n=4 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
41 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
22 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
60 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
22 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
59 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
22 participants
n=5 Participants
|
21 participants
n=7 Participants
|
17 participants
n=5 Participants
|
60 participants
n=4 Participants
|
|
Years from Symptom Onset to Screening
|
2.8 years
STANDARD_DEVIATION 1.7 • n=5 Participants
|
1.9 years
STANDARD_DEVIATION 1.4 • n=7 Participants
|
2.0 years
STANDARD_DEVIATION 1.0 • n=5 Participants
|
2.3 years
STANDARD_DEVIATION 1.5 • n=4 Participants
|
|
Years from Diagnosis to Screening
|
1.3 years
STANDARD_DEVIATION 0.8 • n=5 Participants
|
0.9 years
STANDARD_DEVIATION 0.8 • n=7 Participants
|
1.0 years
STANDARD_DEVIATION 0.8 • n=5 Participants
|
1.1 years
STANDARD_DEVIATION 0.8 • n=4 Participants
|
|
Years from Symptom Onset to Diagnosis
|
1.6 years
STANDARD_DEVIATION 1.5 • n=5 Participants
|
0.9 years
STANDARD_DEVIATION 0.8 • n=7 Participants
|
1.0 years
STANDARD_DEVIATION 0.8 • n=5 Participants
|
1.2 years
STANDARD_DEVIATION 1.1 • n=4 Participants
|
|
Baseline ALS Functional Rating Scale - Revised (ALSFRS-R) Total
|
35.82 Score on a scale
STANDARD_DEVIATION 7.20 • n=5 Participants
|
36.19 Score on a scale
STANDARD_DEVIATION 6.04 • n=7 Participants
|
34.76 Score on a scale
STANDARD_DEVIATION 6.56 • n=5 Participants
|
35.65 Score on a scale
STANDARD_DEVIATION 6.54 • n=4 Participants
|
|
Baseline VC% Predicted Max
|
90.64 % of predicted max value
STANDARD_DEVIATION 20.29 • n=5 Participants
|
86.90 % of predicted max value
STANDARD_DEVIATION 13.92 • n=7 Participants
|
81.71 % of predicted max value
STANDARD_DEVIATION 19.93 • n=5 Participants
|
86.80 % of predicted max value
STANDARD_DEVIATION 18.31 • n=4 Participants
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Creatine 30gm
n=22 Participants
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.
|
Tamoxifen 40mg
n=21 Participants
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.
|
Tamoxifen 80mg
n=17 Participants
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.
|
|---|---|---|---|
|
Change in ALS Functional Rating Scale - Revised (ALSFRS-R)
|
-0.905 scores on a scale
Interval -1.292 to -0.518
|
-0.983 scores on a scale
Interval -1.336 to -0.63
|
-0.743 scores on a scale
Interval -1.259 to -0.227
|
SECONDARY outcome
Timeframe: 38 weeks of treatment followed by a telephone interview at 42 weeks.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.
Outcome measures
| Measure |
Creatine 30gm
n=22 Participants
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.
|
Tamoxifen 40mg
n=21 Participants
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.
|
Tamoxifen 80mg
n=17 Participants
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.
|
|---|---|---|---|
|
Vital Capacity/Pulmonary Function Testing
|
-3.386 Percentage of predicted max value
Interval -4.794 to -1.977
|
-2.915 Percentage of predicted max value
Interval -4.216 to -1.615
|
-3.377 Percentage of predicted max value
Interval -5.203 to -1.552
|
SECONDARY outcome
Timeframe: 38 weeks of treatment followed by a telephone interview at 42 weeks.Secondary efficacy will be assessed by analyzing rate of tracheostomy-free survival at nine months.
Outcome measures
| Measure |
Creatine 30gm
n=22 Participants
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.
|
Tamoxifen 40mg
n=21 Participants
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.
|
Tamoxifen 80mg
n=17 Participants
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.
|
|---|---|---|---|
|
Tracheostomy-free Survival
|
0.455 proportion of participants
Interval 0.276 to 0.679
|
0.286 proportion of participants
Interval 0.14 to 0.528
|
0.412 proportion of participants
Interval 0.222 to 0.675
|
SECONDARY outcome
Timeframe: 38 weeks of treatment followed by a telephone interview at 42 weeks.These events were due to a double-blinded study design.
Outcome measures
| Measure |
Creatine 30gm
n=22 Participants
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.
|
Tamoxifen 40mg
n=21 Participants
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.
|
Tamoxifen 80mg
n=17 Participants
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.
|
|---|---|---|---|
|
Dose Adjustments
Number of Creatine Reductions due to AEs
|
6 Number of Events due to Adverse Events
|
3 Number of Events due to Adverse Events
|
0 Number of Events due to Adverse Events
|
|
Dose Adjustments
Tamoxifen Redutions due to AEs
|
5 Number of Events due to Adverse Events
|
4 Number of Events due to Adverse Events
|
0 Number of Events due to Adverse Events
|
|
Dose Adjustments
Suspensions due to AEs
|
9 Number of Events due to Adverse Events
|
1 Number of Events due to Adverse Events
|
2 Number of Events due to Adverse Events
|
|
Dose Adjustments
Discontinuations due to AEs
|
10 Number of Events due to Adverse Events
|
5 Number of Events due to Adverse Events
|
4 Number of Events due to Adverse Events
|
SECONDARY outcome
Timeframe: 38 weeks of treatment followed by a telephone interview at 42 weeks.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.
Outcome measures
| Measure |
Creatine 30gm
n=22 Participants
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.
|
Tamoxifen 40mg
n=21 Participants
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.
|
Tamoxifen 80mg
n=17 Participants
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.
|
|---|---|---|---|
|
Lab Abnormal Reports by Treatment Assignment
ALT (SGOT)
|
0 Events
|
1 Events
|
0 Events
|
|
Lab Abnormal Reports by Treatment Assignment
Creatinine
|
4 Events
|
0 Events
|
0 Events
|
|
Lab Abnormal Reports by Treatment Assignment
Glucose
|
0 Events
|
0 Events
|
1 Events
|
|
Lab Abnormal Reports by Treatment Assignment
Hematocrit
|
1 Events
|
0 Events
|
0 Events
|
|
Lab Abnormal Reports by Treatment Assignment
Lymphocytes
|
1 Events
|
0 Events
|
0 Events
|
|
Lab Abnormal Reports by Treatment Assignment
MCH
|
1 Events
|
0 Events
|
0 Events
|
|
Lab Abnormal Reports by Treatment Assignment
Neutrophils
|
0 Events
|
0 Events
|
1 Events
|
|
Lab Abnormal Reports by Treatment Assignment
Absolute Neutrophils
|
0 Events
|
0 Events
|
1 Events
|
|
Lab Abnormal Reports by Treatment Assignment
GFR Non-African American
|
2 Events
|
0 Events
|
0 Events
|
|
Lab Abnormal Reports by Treatment Assignment
Potassium
|
0 Events
|
0 Events
|
1 Events
|
|
Lab Abnormal Reports by Treatment Assignment
Red Blood Count (RBC)
|
1 Events
|
0 Events
|
0 Events
|
|
Lab Abnormal Reports by Treatment Assignment
White Blood Count (WBC)
|
1 Events
|
0 Events
|
0 Events
|
SECONDARY outcome
Timeframe: 38 weeks of treatment followed by a telephone interview at 42 weeks.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.
Outcome measures
| Measure |
Creatine 30gm
n=22 Participants
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.
|
Tamoxifen 40mg
n=21 Participants
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.
|
Tamoxifen 80mg
n=17 Participants
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.
|
|---|---|---|---|
|
Hand Held Dynamometry (HHD) Lower Z-score
|
-0.094 Z-score
Interval -0.127 to -0.061
|
-0.067 Z-score
Interval -0.096 to -0.039
|
-0.016 Z-score
Interval -0.052 to 0.02
|
SECONDARY outcome
Timeframe: 38 weeks of treatment followed by a telephone interview at 42 weeks.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.
Outcome measures
| Measure |
Creatine 30gm
n=22 Participants
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.
|
Tamoxifen 40mg
n=21 Participants
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.
|
Tamoxifen 80mg
n=17 Participants
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.
|
|---|---|---|---|
|
HHD Lower % Baseline
|
-9.258 percent change
Interval -13.118 to -5.399
|
-6.711 percent change
Interval -10.302 to -3.121
|
-2.897 percent change
Interval -7.44 to 1.646
|
SECONDARY outcome
Timeframe: 38 weeks of treatment followed by a telephone interview at 42 weeks.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.
Outcome measures
| Measure |
Creatine 30gm
n=22 Participants
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.
|
Tamoxifen 40mg
n=21 Participants
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.
|
Tamoxifen 80mg
n=17 Participants
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.
|
|---|---|---|---|
|
HHD Upper Z-score
|
-0.103 Z-score
Interval -0.159 to -0.048
|
-0.089 Z-score
Interval -0.142 to -0.037
|
-0.039 Z-score
Interval -0.105 to 0.027
|
SECONDARY outcome
Timeframe: 38 weeks of treatment followed by a telephone interview at 42 weeks.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.
Outcome measures
| Measure |
Creatine 30gm
n=22 Participants
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.
|
Tamoxifen 40mg
n=21 Participants
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.
|
Tamoxifen 80mg
n=17 Participants
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.
|
|---|---|---|---|
|
HHD Upper % Baseline
|
-8.451 percent change
Interval -11.726 to -5.175
|
-7.720 percent change
Interval -10.697 to -4.743
|
-4.515 percent change
Interval -8.063 to -0.968
|
SECONDARY outcome
Timeframe: 38 weeks of treatment followed by a telephone interview at 42 weeks.The ATLIS PPN measures are percentages of predicted normal strength based on age, gender, height, and weight using normative data.
Outcome measures
| Measure |
Creatine 30gm
n=22 Participants
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.
|
Tamoxifen 40mg
n=21 Participants
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.
|
Tamoxifen 80mg
n=17 Participants
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.
|
|---|---|---|---|
|
Accurate Test of Limb Isometric Strength (ATLIS) Lower Percentage of Predicted Normal (PPN)
|
-2.098 percentages of predicted normal strength
Interval -3.931 to -0.266
|
-2.375 percentages of predicted normal strength
Interval -4.441 to -0.31
|
-0.491 percentages of predicted normal strength
Interval -2.759 to 1.776
|
SECONDARY outcome
Timeframe: 38 weeks of treatment followed by a telephone interview at 42 weeks.The ATLIS PPN measures are percentages of predicted normal strength based on age, gender, height, and weight using normative data.
Outcome measures
| Measure |
Creatine 30gm
n=22 Participants
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.
|
Tamoxifen 40mg
n=21 Participants
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.
|
Tamoxifen 80mg
n=17 Participants
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.
|
|---|---|---|---|
|
ATLIS Upper Percentage of Predicted Normal (PPN)
|
-1.932 percentages of predicted normal strength
Interval -4.112 to 0.249
|
-1.845 percentages of predicted normal strength
Interval -4.084 to 0.393
|
0.436 percentages of predicted normal strength
Interval -2.143 to 3.016
|
Adverse Events
Creatine 30gm
Serious events: 6 serious events
Other events: 21 other events
Deaths: 0 deaths
Tamoxifen 40mg
Serious events: 3 serious events
Other events: 17 other events
Deaths: 0 deaths
Tamoxifen 80mg
Serious events: 5 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Creatine 30gm
n=22 participants at risk
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.
|
Tamoxifen 40mg
n=21 participants at risk
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.
|
Tamoxifen 80mg
n=17 participants at risk
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.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
0.00%
0/17
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
0.00%
0/17
|
|
Gastrointestinal disorders
Pneumoperitoneum
|
0.00%
0/22
|
4.8%
1/21 • Number of events 1
|
0.00%
0/17
|
|
General disorders
Death
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Hepatobiliary disorders
Cholecystitis Acute
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Metabolism and nutrition disorders
Malnutrition
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
0.00%
0/17
|
|
Nervous system disorders
Subarachnoid Haemorrhage
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
0.00%
0/17
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
0.00%
0/22
|
4.8%
1/21 • Number of events 1
|
5.9%
1/17 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Arrest
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
0.00%
0/17
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Distress
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
0.00%
0/17
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
0.00%
0/22
|
4.8%
1/21 • Number of events 1
|
11.8%
2/17 • Number of events 2
|
|
Vascular disorders
Deep Vein Thrombosis
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
0.00%
0/17
|
Other adverse events
| Measure |
Creatine 30gm
n=22 participants at risk
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.
|
Tamoxifen 40mg
n=21 participants at risk
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.
|
Tamoxifen 80mg
n=17 participants at risk
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.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Eye disorders
Dry Eye
|
9.1%
2/22 • Number of events 2
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Eye disorders
Eye Pain
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal Distention
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal Pain
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
13.6%
3/22 • Number of events 5
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
27.3%
6/22 • Number of events 7
|
23.8%
5/21 • Number of events 5
|
17.6%
3/17 • Number of events 5
|
|
Gastrointestinal disorders
Diarrhoea
|
27.3%
6/22 • Number of events 7
|
14.3%
3/21 • Number of events 8
|
5.9%
1/17 • Number of events 1
|
|
Gastrointestinal disorders
Dry Mouth
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
11.8%
2/17 • Number of events 2
|
|
Gastrointestinal disorders
Dysphagia
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
11.8%
2/17 • Number of events 2
|
|
Gastrointestinal disorders
Gastrooesophageal Reflux Disease
|
9.1%
2/22 • Number of events 2
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
27.3%
6/22 • Number of events 9
|
19.0%
4/21 • Number of events 4
|
11.8%
2/17 • Number of events 3
|
|
Gastrointestinal disorders
Retching
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Gastrointestinal disorders
Salivary Hypersecretion
|
4.5%
1/22 • Number of events 1
|
4.8%
1/21 • Number of events 1
|
5.9%
1/17 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
13.6%
3/22 • Number of events 3
|
4.8%
1/21 • Number of events 1
|
0.00%
0/17
|
|
General disorders
Application Site Rash
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
General disorders
Asthenia
|
9.1%
2/22 • Number of events 2
|
0.00%
0/21
|
23.5%
4/17 • Number of events 4
|
|
General disorders
Chills
|
0.00%
0/22
|
4.8%
1/21 • Number of events 2
|
5.9%
1/17 • Number of events 1
|
|
General disorders
Death
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
General disorders
Fatigue
|
27.3%
6/22 • Number of events 6
|
19.0%
4/21 • Number of events 4
|
41.2%
7/17 • Number of events 7
|
|
General disorders
Oedema Peripheral
|
18.2%
4/22 • Number of events 5
|
9.5%
2/21 • Number of events 2
|
5.9%
1/17 • Number of events 1
|
|
General disorders
Thirst
|
9.1%
2/22 • Number of events 2
|
0.00%
0/21
|
0.00%
0/17
|
|
Hepatobiliary disorders
Cholecystitis Acute
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Infections and infestations
Gastroenteritis Viral
|
9.1%
2/22 • Number of events 2
|
0.00%
0/21
|
0.00%
0/17
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/22
|
4.8%
1/21 • Number of events 1
|
5.9%
1/17 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
0.00%
0/22
|
0.00%
0/21
|
17.6%
3/17 • Number of events 3
|
|
Infections and infestations
Sinusitis
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Infections and infestations
Staphylococcal Infection
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
9.1%
2/22 • Number of events 2
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Infections and infestations
Urinary Tract Infection
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Injury, poisoning and procedural complications
Procedural Pain
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Injury, poisoning and procedural complications
Ankle Fracture
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/22
|
4.8%
1/21 • Number of events 1
|
5.9%
1/17 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fall
|
4.5%
1/22 • Number of events 2
|
9.5%
2/21 • Number of events 2
|
17.6%
3/17 • Number of events 3
|
|
Injury, poisoning and procedural complications
Joint Injury
|
0.00%
0/22
|
9.5%
2/21 • Number of events 2
|
0.00%
0/17
|
|
Injury, poisoning and procedural complications
Post Procedural Haemorrhage
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Injury, poisoning and procedural complications
Skin Laceration
|
9.1%
2/22 • Number of events 2
|
0.00%
0/21
|
0.00%
0/17
|
|
Investigations
Vital Capacity Decreased
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Investigations
Weight Decreased
|
4.5%
1/22 • Number of events 1
|
4.8%
1/21 • Number of events 1
|
5.9%
1/17 • Number of events 1
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
18.2%
4/22 • Number of events 4
|
19.0%
4/21 • Number of events 4
|
5.9%
1/17 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Joint Stiffness
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Mobility Decreased
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
22.7%
5/22 • Number of events 5
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
27.3%
6/22 • Number of events 9
|
14.3%
3/21 • Number of events 3
|
11.8%
2/17 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
9.1%
2/22 • Number of events 2
|
9.5%
2/21 • Number of events 2
|
0.00%
0/17
|
|
Musculoskeletal and connective tissue disorders
Pain in Jaw
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Nervous system disorders
Burning Sensation
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
13.6%
3/22 • Number of events 5
|
9.5%
2/21 • Number of events 4
|
0.00%
0/17
|
|
Nervous system disorders
Dysarthria
|
4.5%
1/22 • Number of events 1
|
4.8%
1/21 • Number of events 1
|
5.9%
1/17 • Number of events 1
|
|
Nervous system disorders
Headache
|
4.5%
1/22 • Number of events 2
|
9.5%
2/21 • Number of events 7
|
11.8%
2/17 • Number of events 2
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 2
|
|
Nervous system disorders
Lethargy
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Nervous system disorders
Muscle Contractions Involuntary
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Nervous system disorders
Peroneal Nerve Palsy
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Psychiatric disorders
Affect Lability
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/22
|
0.00%
0/21
|
11.8%
2/17 • Number of events 2
|
|
Psychiatric disorders
Depression
|
9.1%
2/22 • Number of events 2
|
4.8%
1/21 • Number of events 1
|
11.8%
2/17 • Number of events 2
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/22
|
0.00%
0/21
|
11.8%
2/17 • Number of events 2
|
|
Psychiatric disorders
Mood Swings
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Renal and urinary disorders
Nephrolithiasis
|
9.1%
2/22 • Number of events 2
|
0.00%
0/21
|
0.00%
0/17
|
|
Reproductive system and breast disorders
Vaginal Discharge
|
0.00%
0/22
|
0.00%
0/21
|
11.8%
2/17 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/22
|
4.8%
1/21 • Number of events 1
|
5.9%
1/17 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
4.5%
1/22 • Number of events 1
|
28.6%
6/21 • Number of events 6
|
23.5%
4/17 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Increased Bronchial Secretion
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Increased Upper Airway Secretion
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
0.00%
0/22
|
4.8%
1/21 • Number of events 1
|
5.9%
1/17 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
0.00%
0/22
|
4.8%
1/21 • Number of events 1
|
5.9%
1/17 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Arrest
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
4.5%
1/22 • Number of events 1
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Decubitus Ulcer
|
0.00%
0/22
|
4.8%
1/21 • Number of events 1
|
5.9%
1/17 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Hair Growth Abnormal
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Night Sweats
|
0.00%
0/22
|
4.8%
1/21 • Number of events 1
|
5.9%
1/17 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Surgical and medical procedures
Mole Excision
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Surgical and medical procedures
Tooth Extraction
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
|
Vascular disorders
Deep Vein Thrombosis
|
4.5%
1/22 • Number of events 1
|
9.5%
2/21 • Number of events 2
|
5.9%
1/17 • Number of events 1
|
|
Vascular disorders
Hot Flush
|
0.00%
0/22
|
0.00%
0/21
|
23.5%
4/17 • Number of events 4
|
|
Vascular disorders
Hypotension
|
0.00%
0/22
|
0.00%
0/21
|
5.9%
1/17 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place