Safety and Efficacy Study of Creatine and Tamoxifen in Vo... | NCT01257581

NCT01257581

Status Module

Sponsor/Collaborators Module

Name	Class
ALS Therapy Alliance	OTHER
State University of New York - Upstate Medical University	OTHER

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
creatine	Drug	creatine monohydrate powder	Creatine 30gm
tamoxifen

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Nazem Atassi, MD, MMSc	Masaschusetts General Hospital, Boston, MA	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Kansas Medical Center		Kansas City	Kansas	66160	United States
Massachusetts General Hospital

References Module

Label	URL
Northeast ALS Consortium website	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Efficacy outcomes are adjusted for baseline differences in time from symptom onset to diagnosis, site of symptom onset, and VC.

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00022 BG00121 BG00217 BG00360

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00055.5± 11.4 BG00160.3± 10.6 BG00256.3± 11.3 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0006 BG0014 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0011 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00022 BG00121 BG002

Years from Symptom Onset to Screening

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG0002.8± 1.7 BG0011.9± 1.4 BG002

Years from Diagnosis to Screening

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG0001.3± 0.8 BG0010.9± 0.8 BG002

Years from Symptom Onset to Diagnosis

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG0001.6± 1.5 BG0010.9± 0.8 BG002

Baseline ALS Functional Rating Scale - Revised (ALSFRS-R) Total

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.

Mean

Standard Deviation

Score on a scale

Title

Denominators

Categories

Title	Measurements
	BG00035.82± 7.20 BG001

Baseline VC% Predicted Max

The vital capacity (VC) (percent of predicted normal) was determined using the slow VC method. 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 percent of predicted normal.

Mean

Standard Deviation

% of predicted max value

Title

Denominators

Categories

Title	Measurements
	BG00090.64± 20.29 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

Posted

Mean

95% Confidence Interval

scores on a scale

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

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Units	Counts
Participants	OG00022 OG00121 OG00217

Title

Denominators

Categories

Title	Measurements
	OG000-0.905(-1.292 to -0.518) OG001-0.983(-1.336 to -0.630) OG002-0.743(-1.259 to -0.227)

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.

Posted

Mean

95% Confidence Interval

Percentage of predicted max value

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

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Tracheostomy-free Survival

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

Posted

Number

95% Confidence Interval

proportion of participants

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

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Units	Counts

Secondary

Dose Adjustments

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

Posted

Number

Number of Events due to Adverse Events

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

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Units	Counts

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.

Posted

Number

Events

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

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

Posted

Mean

95% Confidence Interval

Z-score

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

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

Posted

Mean

95% Confidence Interval

percent change

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

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

Posted

Mean

95% Confidence Interval

Z-score

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

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

Posted

Mean

95% Confidence Interval

percent change

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

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

Posted

Mean

95% Confidence Interval

percentages of predicted normal strength

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

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

Posted

Mean

95% Confidence Interval

percentages of predicted normal strength

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

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	6	22	21	22
EG001	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.	3	21	17	21
EG002	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.	5	17	15	17

Serious Adverse Events

Term	Organ System	Statistical Information
Abdominal Pain	Gastrointestinal disorders	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk EG0020 events0 affected17 at risk
Abdominal Pain Upper	Gastrointestinal disorders	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk EG0020 events0 affected17 at risk
Pneumoperitoneum	Gastrointestinal disorders	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk EG0020 events0 affected17 at risk
Death	General disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Cholecystitis Acute	Hepatobiliary disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Pneumonia	Infections and infestations	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Malnutrition	Metabolism and nutrition disorders	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk EG0020 events0 affected17 at risk
Subarachnoid Haemorrhage	Nervous system disorders	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk EG0020 events0 affected17 at risk
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk EG0021 events1 affected17 at risk
Respiratory Arrest	Respiratory, thoracic and mediastinal disorders	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk EG0020 events0 affected17 at risk
Respiratory Distress	Respiratory, thoracic and mediastinal disorders	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk EG0020 events0 affected17 at risk
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk EG0022 events2 affected17 at risk
Deep Vein Thrombosis	Vascular disorders	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk EG0020 events0 affected17 at risk

Other Adverse Events

Term	Organ System	Statistical Information
Leukocytosis	Blood and lymphatic system disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Tinnitus	Ear and labyrinth disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Dry Eye	Eye disorders	EG0002 events2 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Eye Pain	Eye disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Abdominal Distention	Gastrointestinal disorders	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Abdominal Pain	Gastrointestinal disorders	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Abdominal Pain Upper	Gastrointestinal disorders	EG0005 events3 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Constipation	Gastrointestinal disorders	EG0007 events6 affected22 at risk EG0015 events5 affected21 at risk EG0025 events3 affected17 at risk
Diarrhoea	Gastrointestinal disorders	EG0007 events6 affected22 at risk EG0018 events3 affected21 at risk EG0021 events1 affected17 at risk
Dry Mouth	Gastrointestinal disorders	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk EG0022 events2 affected17 at risk
Dysphagia	Gastrointestinal disorders	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk EG0022 events2 affected17 at risk
Gastrooesophageal Reflux Disease	Gastrointestinal disorders	EG0002 events2 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Nausea	Gastrointestinal disorders	EG0009 events6 affected22 at risk EG0014 events4 affected21 at risk EG0023 events2 affected17 at risk
Retching	Gastrointestinal disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Salivary Hypersecretion	Gastrointestinal disorders	EG0001 events1 affected22 at risk EG0011 events1 affected21 at risk EG0021 events1 affected17 at risk
Vomiting	Gastrointestinal disorders	EG0003 events3 affected22 at risk EG0011 events1 affected21 at risk EG0020 events0 affected17 at risk
Application Site Rash	General disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Asthenia	General disorders	EG0002 events2 affected22 at risk EG0010 events0 affected21 at risk EG0024 events4 affected17 at risk
Chills	General disorders	EG0000 events0 affected22 at risk EG0012 events1 affected21 at risk EG0021 events1 affected17 at risk
Death	General disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Fatigue	General disorders	EG0006 events6 affected22 at risk EG0014 events4 affected21 at risk EG0027 events7 affected17 at risk
Oedema Peripheral	General disorders	EG0005 events4 affected22 at risk EG0012 events2 affected21 at risk EG0021 events1 affected17 at risk
Thirst	General disorders	EG0002 events2 affected22 at risk EG0010 events0 affected21 at risk EG0020 events0 affected17 at risk
Cholecystitis Acute	Hepatobiliary disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Gastroenteritis Viral	Infections and infestations	EG0002 events2 affected22 at risk EG0010 events0 affected21 at risk EG0020 events0 affected17 at risk
Nasopharyngitis	Infections and infestations	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk EG0021 events1 affected17 at risk
Pneumonia	Infections and infestations	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0023 events3 affected17 at risk
Sinusitis	Infections and infestations	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Staphylococcal Infection	Infections and infestations	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Upper Respiratory Tract Infection	Infections and infestations	EG0002 events2 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Urinary Tract Infection	Infections and infestations	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Procedural Pain	Injury, poisoning and procedural complications	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Ankle Fracture	Injury, poisoning and procedural complications	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Contusion	Injury, poisoning and procedural complications	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk EG0021 events1 affected17 at risk
Fall	Injury, poisoning and procedural complications	EG0002 events1 affected22 at risk EG0012 events2 affected21 at risk EG0023 events3 affected17 at risk
Joint Injury	Injury, poisoning and procedural complications	EG0000 events0 affected22 at risk EG0012 events2 affected21 at risk EG0020 events0 affected17 at risk
Post Procedural Haemorrhage	Injury, poisoning and procedural complications	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Skin Laceration	Injury, poisoning and procedural complications	EG0002 events2 affected22 at risk EG0010 events0 affected21 at risk EG0020 events0 affected17 at risk
Vital Capacity Decreased	Investigations	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Weight Decreased	Investigations	EG0001 events1 affected22 at risk EG0011 events1 affected21 at risk EG0021 events1 affected17 at risk
Decreased Appetite	Metabolism and nutrition disorders	EG0004 events4 affected22 at risk EG0014 events4 affected21 at risk EG0021 events1 affected17 at risk
Dehydration	Metabolism and nutrition disorders	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Arthritis	Musculoskeletal and connective tissue disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Joint Stiffness	Musculoskeletal and connective tissue disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Mobility Decreased	Musculoskeletal and connective tissue disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Muscle Spasms	Musculoskeletal and connective tissue disorders	EG0005 events5 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Muscular Weakness	Musculoskeletal and connective tissue disorders	EG0009 events6 affected22 at risk EG0013 events3 affected21 at risk EG0022 events2 affected17 at risk
Neck Pain	Musculoskeletal and connective tissue disorders	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Pain in Extremity	Musculoskeletal and connective tissue disorders	EG0002 events2 affected22 at risk EG0012 events2 affected21 at risk EG0020 events0 affected17 at risk
Pain in Jaw	Musculoskeletal and connective tissue disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Tendonitis	Musculoskeletal and connective tissue disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Burning Sensation	Nervous system disorders	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Dizziness	Nervous system disorders	EG0005 events3 affected22 at risk EG0014 events2 affected21 at risk EG0020 events0 affected17 at risk
Dysarthria	Nervous system disorders	EG0001 events1 affected22 at risk EG0011 events1 affected21 at risk EG0021 events1 affected17 at risk
Headache	Nervous system disorders	EG0002 events1 affected22 at risk EG0017 events2 affected21 at risk EG0022 events2 affected17 at risk
Hypoaesthesia	Nervous system disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0022 events1 affected17 at risk
Lethargy	Nervous system disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Muscle Contractions Involuntary	Nervous system disorders	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Peroneal Nerve Palsy	Nervous system disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Affect Lability	Psychiatric disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Anxiety	Psychiatric disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0022 events2 affected17 at risk
Depression	Psychiatric disorders	EG0002 events2 affected22 at risk EG0011 events1 affected21 at risk EG0022 events2 affected17 at risk
Insomnia	Psychiatric disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0022 events2 affected17 at risk
Mood Swings	Psychiatric disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Nephrolithiasis	Renal and urinary disorders	EG0002 events2 affected22 at risk EG0010 events0 affected21 at risk EG0020 events0 affected17 at risk
Vaginal Discharge	Reproductive system and breast disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0022 events2 affected17 at risk
Cough	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk EG0021 events1 affected17 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	EG0001 events1 affected22 at risk EG0016 events6 affected21 at risk EG0024 events4 affected17 at risk
Increased Bronchial Secretion	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Increased Upper Airway Secretion	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Nasal Congestion	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk EG0021 events1 affected17 at risk
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk EG0021 events1 affected17 at risk
Respiratory Arrest	Respiratory, thoracic and mediastinal disorders	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Alopecia	Skin and subcutaneous tissue disorders	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Decubitus Ulcer	Skin and subcutaneous tissue disorders	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk EG0021 events1 affected17 at risk
Hair Growth Abnormal	Skin and subcutaneous tissue disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Night Sweats	Skin and subcutaneous tissue disorders	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk EG0021 events1 affected17 at risk
Pruritis	Skin and subcutaneous tissue disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Mole Excision	Surgical and medical procedures	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Tooth Extraction	Surgical and medical procedures	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk
Deep Vein Thrombosis	Vascular disorders	EG0001 events1 affected22 at risk EG0012 events2 affected21 at risk EG0021 events1 affected17 at risk
Hot Flush	Vascular disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0024 events4 affected17 at risk
Hypotension	Vascular disorders	EG0000 events0 affected22 at risk EG0010 events0 affected21 at risk EG0021 events1 affected17 at risk

ID	Term
D000690	Amyotrophic Lateral Sclerosis

Ancestor Terms

ID	Term
D013118	Spinal Cord Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D016472	Motor Neuron Disease
D019636	Neurodegenerative Diseases
D057177	TDP-43 Proteinopathies
D009468	Neuromuscular Diseases
D057165	Proteostasis Deficiencies
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

ID	Term
D003401	Creatine
D013629	Tamoxifen

Ancestor Terms

ID	Term
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D013267	Stilbenes
D001597	Benzylidene Compounds
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons

Units	Counts
Participants	OG00022 OG00121 OG00217

Units	Counts
Participants	OG00022 OG00121 OG00217

Units	Counts
Participants	OG00022 OG00121 OG00217

Units	Counts
Participants	OG00022 OG00121 OG00217