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

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.

Study Overview

• Status: Recruiting
• Conditions: Safety
• Intervention / Treatment: Dietary supplement: Celastrol

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.

• Study Type: Interventional
• Enrollment (Anticipated): 35
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rubin Patel, MD; Phone Number: 225-224-8690; Email: rubin@patientplusuc.com
• Study Contact Backup: Name: Sarah Carabello, B.A.; Phone Number: 225-716-2297; Email: scabal4@lsu.edu

Study Locations

• United States
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70810
      • Recruiting
      • Patient Plus Urgent Care
      • Contact: Rubin Patel, MD; Phone Number: 225-224-8690; Email: medicalresearch@patientplusuc.com
      • Contact: Sarah Carabello, BA; Phone Number: 2257162297; Email: scabal4@lsu.edu
      • Principal Investigator: Rubin Patel, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 36 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amount of Celastrol Administered; Chronic evaluation of the same doses of Celastrol to each subject over 90-day period	Dietary supplement: Celastrol; same dose of Celastrol will be given every day for a period of 90-days to all participants.; Other Names: 24,25,26-trinoroleana-1(10),3,5,7- tetraen-29-oic acid; 34157-83-0

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Legend Labz, Inc.
• Investigators: Principal Investigator: Rubin Patel, MD, Patient Plus Urgent Care

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2022
• Primary Completion (Anticipated): May 25, 2023
• Study Completion (Anticipated): May 25, 2023

Study Registration Dates

• First Submitted: August 8, 2022
• First Submitted That Met QC Criteria: August 8, 2022
• First Posted (Actual): August 9, 2022

Study Record Updates

• Last Update Posted (Actual): August 9, 2022
• Last Update Submitted That Met QC Criteria: August 8, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: AMT-002-2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Averages of collective patient data
• IPD Sharing Time Frame: 1 year
• IPD Sharing Access Criteria: All data available on clinicaltrials.gov
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No