Autophagy Activator for Type 2 Diabetes

Recruiting in Palo Alto (17 mi)

Overseen by William Hughes, Ph.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Medical College of Wisconsin

Must not be taking: Anticoagulants, Antiplatelets, Steroids, others

Disqualifiers: Hypertension, Tobacco use, Heart failure, others

Trial Summary

What is the purpose of this trial?

This trial tests whether a sugar called trehalose can help improve small blood vessel function in adults with Type 2 Diabetes. Participants will take trehalose for a short period. Trehalose helps cells clean out damaged parts, which may help blood vessels relax and widen more easily. Trehalose is a naturally occurring disaccharide that has been found to improve glucose metabolism and homeostasis in different diabetes models.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using certain drugs like anti-coagulants, anti-platelet drugs, or steroids. It's best to discuss your specific medications with the trial coordinators.

What evidence supports the effectiveness of the drug trehalose for treating type 2 diabetes?

Research shows that trehalose can activate autophagy (a process where cells clean out damaged components) and reduce blood sugar levels in diabetic mice, suggesting it may help manage type 2 diabetes. ^{1 2 3 4 5}

Is trehalose safe for human use?

Trehalose, a natural sugar, has been used widely as a food additive and preservative with minimal toxicity reported. Studies show it can activate autophagy (a process that cleans out damaged cells) and has been used safely in various research contexts, including diabetes and liver conditions. ^{1 2 4 5 6}

How does the drug trehalose work for type 2 diabetes?

Trehalose is unique because it activates autophagy (a process that cleans out damaged cells) without affecting mTOR (a protein that regulates cell growth), which is different from many other diabetes treatments. It also helps reduce blood sugar levels and inflammation, making it a promising option for managing type 2 diabetes. ^{1 2 3 5 7}

Research Team

William Hughes, Ph.D.

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

Adults aged 18-80 with Type 2 Diabetes as per ADA guidelines or healthy individuals with no more than one cardiovascular risk factor can join. Exclusions include those on erectile dysfunction meds, steroids, or hormone therapies recently; heart failure patients; BMI over 35; tobacco users in the last six months; and several other conditions.

Inclusion Criteria

I have been diagnosed with Type 2 Diabetes following ADA guidelines.

I am generally healthy with no more than one risk for heart disease.

I am between 18 and 80 years old.

Exclusion Criteria

I have kidney problems.

I have Type 1 Diabetes.

I have a history of retinopathy.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either trehalose or placebo for 14 days to assess the role of autophagy in microvascular function

2 weeks

2 study days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• Placebo (Other)
• Trehalose (Other)

Trial Overview This study is testing if trehalose, a sugar that may activate autophagy (cellular cleanup), improves blood vessel function in people with Type 2 Diabetes compared to a placebo. Participants will have their microvascular function tested before and after two weeks of taking either trehalose or placebo.

Participant Groups

Group I: Trehalose Experimental Treatment 1 Intervention

10g mixed in 500 mL of water, consumed 1 time per day

Group II: Placebo Placebo Group 1 Intervention

10g microcrystalline cellulose in 500 mL, consumed 1 time per day

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Dr. Joseph E. Kerschner

Medical College of Wisconsin

Chief Medical Officer since 2011

MD, specific institution not identified

Dr. John R. Raymond, Sr.

Medical College of Wisconsin

Chief Executive Officer since 2010

MD from the Medical University of South Carolina

Findings from Research

Trehalose, a natural compound, effectively induces autophagy in neural stem cells and is as potent as rapamycin and starvation in promoting autophagosome formation, which is crucial for cellular health.

In conditions of high glucose and maternal diabetes, trehalose not only reverses the suppression of autophagy but also enhances the removal of damaged organelles, suggesting its therapeutic potential in preventing autophagy-related disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trehalose restores functional autophagy suppressed by high glucose. Xu, C., Chen, X., Sheng, WB., et al.[2020]

Trehalose is a promising autophagy inducer with minimal side effects, approved for human use, that shows potential in treating neurodegenerative diseases by reducing neurotoxic protein accumulation and enhancing antioxidant defenses.

In animal models of Alzheimer's, Parkinson's, and Huntington's diseases, trehalose demonstrated neuroprotective effects, suggesting it could be an effective multitarget therapy for neurodegeneration, warranting further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disaccharide trehalose in experimental therapies for neurodegenerative disorders: Molecular targets and translational potential. Pupyshev, AB., Klyushnik, TP., Akopyan, AA., et al.[2022]

Trehalose has shown promise in reducing the burden of cardiometabolic diseases, such as atherosclerosis and insulin resistance, in various animal models, indicating its potential as a therapeutic agent.

The beneficial effects of trehalose are linked to its ability to activate autophagy and other fasting-like processes, although its efficacy can vary based on how it is administered and the specific disease context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using trehalose to prevent and treat metabolic function: effectiveness and mechanisms. Zhang, Y., DeBosch, BJ.[2022]

Trehalose, a natural disaccharide, effectively induces autophagy in keratinocytes, as demonstrated by increased conversion of LC3-I to LC3-II and the formation of autophagic vacuoles in human keratinocyte cell lines and primary keratinocytes.

Unlike other saccharides, trehalose activates autophagy through an mTOR-independent pathway and offers cytoprotection against UVB radiation, although it also inhibits cell proliferation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trehalose, sucrose and raffinose are novel activators of autophagy in human keratinocytes through an mTOR-independent pathway. Chen, X., Li, M., Li, L., et al.[2022]

References

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

Trehalose restores functional autophagy suppressed by high glucose. [2020]

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

Trehalose inhibits solute carrier 2A (SLC2A) proteins to induce autophagy and prevent hepatic steatosis. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Disaccharide trehalose in experimental therapies for neurodegenerative disorders: Molecular targets and translational potential. [2022]

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

Using trehalose to prevent and treat metabolic function: effectiveness and mechanisms. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Trehalose Activates Hepatic and Myocardial Autophagy and Has Anti-Inflammatory Effects in db/db Diabetic Mice. [2022]

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

Sweet taste receptor agonists attenuate macrophage IL-1β expression and eosinophilic inflammation linked to autophagy deficiency in myeloid cells. [2022]

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

Trehalose, sucrose and raffinose are novel activators of autophagy in human keratinocytes through an mTOR-independent pathway. [2022]