A Sub-Chronic Evaluation of the Safety of Celastrol in Human Subjects

Study Overview
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Brief Summary
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This is an open label safety study that will not be blinded or placebo controlled. Purpose is to evaluate the safety of Celastrol in healthy men and women volunteers, between 18 and 40 years of age, over a 90-day period. Celastrol is different than Cholesterol. Cholesterol is a risk for heart disease. Celastrol is a natural occurring compound extracted from the root of Tripterygium wilfordii, a herb used in Chinese medicine.

Detailed Description
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Pre-study Visit A pre-study visit will occur approximately one week before the scheduled beginning of the study. At this time all nutritional supplements must be stopped. During this visit, the subjects will sign an Informed Consent, will provide a medical history and list their concurrent medications. They will have a physical exam and then have a blood sample taken and receive an EKG. Women of child-bearing age will provide a urine sample to test for pregnancy. The subjects will then have their eligibility assessed based on the inclusion/exclusion criteria. Study Visit 1, Day 0 The subjects who meet the entrance criteria will arrive at the clinic at an appointed time, and will again have their concurrent medications reviewed. They will be assigned a unique study number and be given a vial of experimental product that contains the same number as the subject, and contains ten capsules of product. Each capsule will contain  67 mg of Celastrol. Instructions on how and when to take the experimental product will be given to the subjects by the clinician. A log book or an electronic portal will be presented to each subject so that daily information, such as the day and time of product ingestion, and any self-perceived adverse events, will be recorded. Any self-perceived adverse events experienced prior to taking any product should be told to the clinician at this time. The subjects will be instructed to bring their drug vials to every clinic visit so that compliance can be determined. Any subject who has less than an 80% compliance rate will be excused from the study. Study Visit 2, Day 2 To test for any acute effects of the experimental product, the subjects will return to the clinic on day 2 of the study. A blood sample will be taken, the log-book and vial will be reviewed for compliance, concurrent medications and any self-perceived adverse events will be discussed. Their vials that were given on Study Day 1 will contain enough remaining experimental product capsules to support the study to Day 7. Three extra capsules will be provided in the event that the subject cannot return to the clinic on the exact day indicated. Study Visit 3, Day 7 The subjects will return to the clinic on Day 7, and a blood sample will be taken. As before, the log-book and vial will be reviewed for compliance, and concurrent medications and any self-perceived adverse events will be discussed. A vial containing enough experimental product, plus three additional capsules, to last another 7 days will be given. Study Visit 4, Day 14 The clinic visit on Day 14 will mimic the visit on Day 7. However, during this visit the subjects will also receive a physical exam with vital signs, and an EKG. A vial containing enough product to last until Day 28 (Visit 5), plus 5 additional capsules, will be given to each subject. Study Visits 5 and 6, Days 28 and 58 The clinic visits on Days 28 and 58 will again mimic the visit on Day 7. No EKGs will be taken. On Day 28, vials containing enough product, plus 5 additional capsules, to last to day 58 (Visit 6) will be given to each subject. Study Visit 7, Day 88 The final clinic visit will consist of a physical exam with vital signs, a blood sample, and an EKG. The logbook and vial will be reviewed for compliance, and concurrent medications and any self-perceived adverse events will be discussed. At this point the study is complete and the subjects are released.

Official Title
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A Sub-Chronic Evaluation of the Safety of Celastrol in Human Subjects

Conditions
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Safety

Intervention / Treatment
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* Dietary Supplement: Celastrol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals who are between 18 and 40 years of age and who are found to be healthy without any underlying medical conditions and are not taking any daily medications. This does not exclude patients who take drugs prn. Individuals who have not be involved in other clinical trials during the last 45 days. However, individuals that participated in the Celastrol-Sperm Health study can enter the trial after a seven day wash-out period Women of child-bearing age and ability who agree to abstain from sexual intercourse, or agree to use condoms or vaginal diaphragms or other devices designed to prevent pregnancy; or are taking hormonal medication designed to prevent pregnancy, during the entire course of the study. Women with tubal ligations or other physical conditions that make it impossible to conceive. Women who are not pregnant or breast-feeding. Exclusion Criteria: Individuals who have been involved in any other clinical trial during the last 45 days. Women of child-bearing age who do not agree to abstain from sexual intercourse, or do not agree to use condoms or vaginal diaphragms or other devices designed to prevent pregnancy, or who are not on hormonal medication designed to prevent pregnancy, during the entire course of the study. Women who are pregnant or breast-feeding Clinically significant cardiac disease including uncontrolled congestive heart failure and unstable angina Individuals on medications that the clinician feels may interfere with the results Medications that might interfere with blood chemistry, CBCs, or vital signs. Subjects who are taking daily medications. The use of therapies prn, such as headache and allergy medication are allowed. Subjects Less than 18 years of age Prisoners Subjects who have taken anabolic steroid use during the last six months. Subjects with a current history of addictive alcohol or illegal drug abuse (e.g. cocaine, heroin, etc.). The use of marijuana is allowed.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Sequential Assignment
Interventional Model Description: healthy men and women volunteers, between 18 and 40 years of age, over a 90-day period.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amount of Celastrol Administered<br>Chronic evaluation of the same doses of Celastrol to each subject over 90-day period | Dietary Supplement: Celastrol<br>* same dose of Celastrol will be given every day for a period of 90-days to all participants.<br>* Other names: 34157-83-0;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of celastrol on the function of the liver | Absence of Toxicity, as determined by comparison of periodic subject data to their baseline data | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EKG evaluation | Compared to laboratory standards | 90 days | 
| Glucose (MG/DL) | Glucose levels measured in the blood | 90 days | 
| BUN (MG/DL) | BUN levels measured in the blood | 90 days | 
| Creatine (MG/DL) | Creatine levels measured in the blood | 90 days | 
| eGFR (ML/MIN/1.73) | eGFR levels measured in the blood | 90 days | 
| CALC BUN/CREAT (Ratio) | Ratio of CALC BUN/CREAT measured in the blood | 90 days | 
| Sodium (MEQ/L) | Sodium levels measured in the blood | 90 days | 
| Potassium (MEQ/L) | Potassium levels measured in the blood | 90 days | 
| Chloride (MEQ/L) | Chloride levels measured in the blood | 90 days | 
| Carbon Dioxide (MEQ/L) | Carbon Dioxide levels measured in the blood | 90 days | 
| Calcium (MG/DL) | Calcium levels measured in the blood | 90 days | 
| Protein, Total (G/DL) | Total Protein levels measured in the blood | 90 days | 
| Albumin (G/DL) | Albumin levels measured in the blood | 90 days | 
| CALC Globulin (G/DL) | CALC Globulin levels measured in the blood | 90 days | 
| CALC A/G (Ratio) | Ratio of CALC A/G levels measured in the blood | 90 days | 
| Bilirubin, Total (MG/DL) | Bilirubin levels measured in the blood | 90 days | 
| Alkaline Phosphatase (U/L) | Alkaline Phosphatase levels measured in the blood | 90 days | 
| AST (U/L) | AST levels measured in the blood | 90 days | 
| ALT (U/L) | ALT levels measured in the blood | 90 days | 
| WBC (K/UL) | WBC levels measured in the blood | 90 days | 
| RBC (M/UL) | RBC levels measured in the blood | 90 days | 
| Hemoglobin (G/DL) | Hemoglobin levels measured in the blood | 90 days | 
| Hematocrit (%) | Hematocrit levels measured in the blood | 90 days | 
| MCV (fL) | MCV levels measured in the blood | 90 days | 
| MCH (PG) | MCH levels measured in the blood | 90 days | 
| MCHC (G/DL) | MCHC levels measured in the blood | 90 days | 
| RDW (%) | RDW levels measured in the blood | 90 days | 
| Neutrophils (%) | Neutrophils levels measured in the blood | 90 days | 
| Lymphocytes (%) | Lymphocytes levels measured in the blood | 90 days | 
| Monocytes (%) | Monocytes levels measured in the blood | 90 days | 
| Eosinophils (%) | Eosinophils levels measured in the blood | 90 days | 
| Basophils (%) | Basophils levels measured in the blood | 90 days | 
| Immature Granulocytes (%) | Immature Granulocytes levels measured in the blood | 90 days | 
| Nucleated RBCS (/100 WBC'S) | Nucleated RBCS levels measured in the blood | 90 days | 
| Platelet Count (K/UL) | Platelet Count levels measured in the blood | 90 days | 
| Absolute Neutrophils (K/UL) | Absolute Neutrophils levels measured in the blood | 90 days | 
| Absolute Monocytes (K/UL) | Absolute Monocytes levels measured in the blood | 90 days | 
| Absolute Eosinophils (K/UL) | Absolute Eosinophils levels measured in the blood | 90 days | 
| Absolute Basophils (K/UL) | Absolute Basophils levels measured in the blood | 90 days | 
| Absolute Immature Granulocytes (K/UL) | Absolute Immature Granulocyte levels measured in the blood | 90 days | 
| Absolute Nucleated RBCS (K/UL) | Absolute Nucleated RBCS levels measured in the blood | 90 days | 
| MPV (fL) | MPV levels measured in the blood | 90 days |