Clinical trial NCT05494112: A Sub-Chronic Evaluation of the Safety of Celastrol in Human Subjects
Official title: A Sub-Chronic Evaluation of the Safety of Celastrol in Human Subjects
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Safety
Lead sponsor: Legend Labz, Inc.
Sponsor class: INDUSTRY
First posted: 2022-08-09
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: healthy men and women volunteers, between 18 and 40 years of age, over a 90-day period.
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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
3. 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.
4. Women with tubal ligations or other physical conditions that make it impossible to conceive.
5. Women who are not pregnant or breast-feeding.

Exclusion Criteria:

1. Individuals who have been involved in any other clinical trial during the last 45 days.
2. 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.
3. Women who are pregnant or breast-feeding
4. Clinically significant cardiac disease including uncontrolled congestive heart failure and unstable angina
5. Individuals on medications that the clinician feels may interfere with the results
6. Medications that might interfere with blood chemistry, CBCs, or vital signs.
7. Subjects who are taking daily medications. The use of therapies prn, such as headache and allergy medication are allowed.
8. Subjects Less than 18 years of age
9. Prisoners
10. Subjects who have taken anabolic steroid use during the last six months.
11. Subjects with a current history of addictive alcohol or illegal drug abuse (e.g. cocaine, heroin, etc.). The use of marijuana is allowed.

Primary outcomes:
measure: The effect of celastrol on the function of the liver
timeFrame: 90 days
Secondary outcomes:
measure: EKG evaluation
timeFrame: 90 days
measure: Glucose (MG/DL)
timeFrame: 90 days
measure: BUN (MG/DL)
timeFrame: 90 days
measure: Creatine (MG/DL)
timeFrame: 90 days
measure: eGFR (ML/MIN/1.73)
timeFrame: 90 days
measure: CALC BUN/CREAT (Ratio)
timeFrame: 90 days
measure: Sodium (MEQ/L)
timeFrame: 90 days
measure: Potassium (MEQ/L)
timeFrame: 90 days
measure: Chloride (MEQ/L)
timeFrame: 90 days
measure: Carbon Dioxide (MEQ/L)
timeFrame: 90 days
measure: Calcium (MG/DL)
timeFrame: 90 days
measure: Protein, Total (G/DL)
timeFrame: 90 days
measure: Albumin (G/DL)
timeFrame: 90 days
measure: CALC Globulin (G/DL)
timeFrame: 90 days
measure: CALC A/G (Ratio)
timeFrame: 90 days
measure: Bilirubin, Total (MG/DL)
timeFrame: 90 days
measure: Alkaline Phosphatase (U/L)
timeFrame: 90 days
measure: AST (U/L)
timeFrame: 90 days
measure: ALT (U/L)
timeFrame: 90 days
measure: WBC (K/UL)
timeFrame: 90 days
measure: RBC (M/UL)
timeFrame: 90 days
measure: Hemoglobin (G/DL)
timeFrame: 90 days
measure: Hematocrit (%)
timeFrame: 90 days
measure: MCV (fL)
timeFrame: 90 days
measure: MCH (PG)
timeFrame: 90 days
measure: MCHC (G/DL)
timeFrame: 90 days
measure: RDW (%)
timeFrame: 90 days
measure: Neutrophils (%)
timeFrame: 90 days
measure: Lymphocytes (%)
timeFrame: 90 days
measure: Monocytes (%)
timeFrame: 90 days
measure: Eosinophils (%)
timeFrame: 90 days
measure: Basophils (%)
timeFrame: 90 days
measure: Immature Granulocytes (%)
timeFrame: 90 days
measure: Nucleated RBCS (/100 WBC'S)
timeFrame: 90 days
measure: Platelet Count (K/UL)
timeFrame: 90 days
measure: Absolute Neutrophils (K/UL)
timeFrame: 90 days
measure: Absolute Monocytes (K/UL)
timeFrame: 90 days
measure: Absolute Eosinophils (K/UL)
timeFrame: 90 days
measure: Absolute Basophils (K/UL)
timeFrame: 90 days
measure: Absolute Immature Granulocytes (K/UL)
timeFrame: 90 days
measure: Absolute Nucleated RBCS (K/UL)
timeFrame: 90 days
measure: MPV (fL)
timeFrame: 90 days
Other outcomes:
Locations:
city: Baton Rouge
country: United States
facility: Patient Plus Urgent Care
state: Louisiana
Study officials:
affiliation: Patient Plus Urgent Care
name: Rubin Patel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kusy S, Ghosn EE, Herzenberg LA, Contag CH. Development of B cells and erythrocytes is specifically impaired by the drug celastrol in mice. PLoS One. 2012;7(4):e35733. doi: 10.1371/journal.pone.0035733. Epub 2012 Apr 24.
citation: Hou W, Liu B, Xu H. Celastrol: Progresses in structure-modifications, structure-activity relationships, pharmacology and toxicology. Eur J Med Chem. 2020 Mar 1;189:112081. doi: 10.1016/j.ejmech.2020.112081. Epub 2020 Jan 20.
citation: Sun H, Liu X, Xiong Q, Shikano S, Li M. Chronic inhibition of cardiac Kir2.1 and HERG potassium channels by celastrol with dual effects on both ion conductivity and protein trafficking. J Biol Chem. 2006 Mar 3;281(9):5877-84. doi: 10.1074/jbc.M600072200. Epub 2006 Jan 11.
citation: Sun M, Tang Y, Ding T, Liu M, Wang X. Inhibitory effects of celastrol on rat liver cytochrome P450 1A2, 2C11, 2D6, 2E1 and 3A2 activity. Fitoterapia. 2014 Jan;92:1-8. doi: 10.1016/j.fitote.2013.10.004. Epub 2013 Oct 19.
citation: Wang S, Liu K, Wang X, He Q, Chen X. Toxic effects of celastrol on embryonic development of zebrafish (Danio rerio). Drug Chem Toxicol. 2011 Jan;34(1):61-5. doi: 10.3109/01480545.2010.494664. Epub 2010 Oct 18.
citation: Yuan YY, Gu ZP, Shi QX, Qin GW, Xu RS, Cao L. [In vitro inhibition of celastrol on spermatozoa fertilization ability of guinea pig]. Yao Xue Xue Bao. 1995;30(5):331-5. Chinese.
citation: Zhang YS, Tu YY, Gao XC, Yuan J, Li G, Wang L, Deng JP, Wang Q, Ma RM. Strong inhibition of celastrol towards UDP-glucuronosyl transferase (UGT) 1A6 and 2B7 indicating potential risk of UGT-based herb-drug interaction. Molecules. 2012 Jun 5;17(6):6832-9. doi: 10.3390/molecules17066832.