Study of Harmine in Healthy Subjects

Overseen By Leah Israel

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: James Murrough

Must not be taking: Psychotropics, Antidepressants, Benzodiazepines, others

Disqualifiers: Cancer, Stroke, Seizures, Psychiatric, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing harmine to find out how much can be safely given to people. Healthy volunteers will receive one amount of harmine, and researchers will check for any side effects. The information will help decide the next amount for the next person.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications. The trial does not allow medications that affect the central nervous system or cardiovascular system, as well as some over-the-counter drugs and herbal remedies. It's best to discuss your current medications with the trial team to see if they are allowed.

Is Harmine Hydrochloride generally safe for humans?

The available research does not provide specific safety data for Harmine Hydrochloride Capsules. However, general drug safety data suggests that while many drugs are safe, some can have serious side effects, and safety advisories are issued for emerging harms. It's important to consult healthcare professionals for personalized advice. ^{1 2 3 4 5}

How does the drug Harmine Hydrochloride Capsules differ from other treatments for cancer?

Harmine Hydrochloride Capsules are unique because they have shown the ability to inhibit cancer cell growth in a time-dose-dependent manner, and they can be administered locally to reduce side effects, unlike systemic treatments that may cause central nervous toxicity. This local administration allows for prolonged drug presence at the tumor site, potentially enhancing its effectiveness. ^{6 7 8 9 10}

Who Is on the Research Team?

James Murrough, MD, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

Inclusion Criteria

Your body mass index (BMI) falls between 19 and 30.

Women must not be breastfeeding

Women of childbearing potential and men must be using an acceptable method of contraception to avoid pregnancy throughout the study as judged by the investigator

Exclusion Criteria

Children under the age of 18 and adults over the age of 55 due to concerns regarding neurodevelopmental and neurocognitive effects, respectively

Presence or history of psychiatric disorder as diagnosed by Mini Neuropsychiatric Interview (MINI)

Urine toxicology positive for illicit drugs or dis-allowed concomitant medications as per study protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single oral dose of harmine in a dose escalation design

1 day

1 visit (in-person)

Monitoring

Participants are monitored for adverse events and dose limiting toxicities for 24 hours post-dosing

24 hours

Continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Harmine Hydrochloride Capsules

How Is the Trial Designed?

Group I: Harmine Dose Experimental Treatment 1 Intervention

There will be a total of seven possible doses that include 100 mg, 200 mg, 300 mg, 500 mg, 700 mg, 900 mg and 1200 mg. Each study subject will receive a single oral dose of harmine in this single ascending dose design.

Who Is Running the Clinical Trial?

James Murrough

Lead Sponsor

Trials

9

Recruited

250+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

An international study found that 70% of adverse drug events in humans were predicted by animal studies, indicating a good correlation between animal and human toxicity assessments.

While animal studies effectively identified many toxic effects, certain severe adverse events, like immuno-allergies, were not detected, highlighting the need for improved predictive tools in drug safety evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Are non-clinical studies predictive of adverse events in humans?]. Claude, N.[2019]

The safety of marketed drugs is a significant concern, as some commonly prescribed medications can lead to serious or life-threatening side effects in patients.

The ChEMBL resource will provide a curated drug safety data set, including toxicity classifications and black box warnings, which will be freely available and regularly updated to aid in drug safety research and discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. Hunter, FMI., Bento, AP., Bosc, N., et al.[2023]

Between 2010 and 2016, 164 safety advisories regarding cardiac-related adverse events were issued by regulators in Australia, Canada, the UK, and the US, highlighting the prevalence of risks associated with 61 different drugs, primarily involving cardiac arrhythmias and coronary artery disorders.

While monitoring patients was the most common recommendation in these advisories, only 41.2% provided detailed guidance on how to conduct this monitoring, indicating a need for more consistent and comprehensive information for healthcare professionals and consumers regarding rare but serious medication harms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulatory post-market drug safety advisories on cardiac harm: A comparison of four national regulatory agencies. Hooimeyer, A., Bhasale, A., Perry, L., et al.[2023]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Safety profile of H1-antihistamines in pediatrics: an analysis based on data from VigiBase. [2018]

2. France pubmed.ncbi.nlm.nih.gov

[Are non-clinical studies predictive of adverse events in humans?]. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Non-cardiac adverse effects of antihistamines (H1-receptor antagonists). [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Regulatory post-market drug safety advisories on cardiac harm: A comparison of four national regulatory agencies. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

The impact of Harmine hydrochloride on growth, apoptosis and migration, invasion of gastric cancer cells. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Synthesis and biological evaluation of N(9)-substituted harmine derivatives as potential anticancer agents. [2017]

8. United States pubmed.ncbi.nlm.nih.gov

Improving anti-tumor outcomes for colorectal cancer therapy through in situ thermosensitive gel loading harmine. [2020]

9. England pubmed.ncbi.nlm.nih.gov

The transdermal performance, pharmacokinetics, and anti-inflammatory pharmacodynamics evaluation of harmine-loaded ethosomes. [2020]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Synthesis of New Harmine Isoxazoles and Evaluation of their Potential Anti-Alzheimer, Anti-inflammatory, and Anticancer Activities. [2019]