Autophagy Activator for Type 2 Diabetes

Overseen By William Hughes, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Medical College of Wisconsin

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

Disqualifiers: Hypertension, Tobacco use, Heart failure, others

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how autophagy, the body's process for cleaning out damaged cells, affects blood vessel health in people with Type 2 Diabetes. Participants will take either trehalose, a sugar that might boost autophagy, or a placebo. Researchers will then assess the impact on blood vessels. The trial is open to individuals with Type 2 Diabetes and healthy participants with no more than one heart risk factor. As an Early Phase 1 trial, this research aims to understand how trehalose works in people, offering participants a chance to contribute to groundbreaking science.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that trehalose, the treatment being tested in this trial, is generally safe for people. In previous studies, participants took trehalose for up to 12 weeks without significant side effects. Even when consumed in large amounts in diets, no consistent or dose-related negative effects were reported, indicating that trehalose is well-tolerated. Additionally, it has been found to improve how the body handles sugar, benefiting those at risk of type 2 diabetes. Overall, trehalose appears to be a safe choice for this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Type 2 Diabetes?

Researchers are excited about Trehalose as a treatment for Type 2 Diabetes because it works by activating autophagy, a natural process that helps clean out damaged cells and regenerate healthier ones. Unlike current treatments such as metformin or insulin, which primarily focus on controlling blood sugar levels, Trehalose targets cell maintenance and health at a deeper cellular level. This novel mechanism could offer a fresh approach to managing the disease, potentially improving outcomes for patients by addressing underlying cellular dysfunctions.

What evidence suggests that trehalose might be an effective treatment for Type 2 Diabetes?

Research has shown that trehalose, a natural sugar, might help control blood sugar levels, particularly for those at risk of type 2 diabetes. In earlier studies, participants who consumed trehalose daily for 12 weeks demonstrated better glucose tolerance, meaning their bodies managed sugar more effectively. Other studies found that trehalose helped prevent weight gain and improved insulin efficiency in lowering blood sugar. Animal studies also showed that trehalose could prevent some symptoms of metabolic disorders, such as difficulty managing sugar levels. Overall, these findings suggest that trehalose might aid in managing blood sugar and related issues. In this trial, participants will receive either trehalose or a placebo to evaluate its effectiveness in managing type 2 diabetes. ^{1 5 6 7 8}

Who Is on the Research Team?

William Hughes, Ph.D.

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

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.

Exclusion Criteria

I have kidney problems.

I have Type 1 Diabetes.

I have a history of retinopathy.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Trehalose

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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]

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 treatment in db/db mice led to significant reductions in blood glucose levels and glycated hemoglobin, indicating its potential efficacy in managing diabetes.

The treatment also enhanced autophagy in the liver and heart, suggesting that activating lipophagy could be a promising therapeutic approach for diabetes-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trehalose Activates Hepatic and Myocardial Autophagy and Has Anti-Inflammatory Effects in db/db Diabetic Mice. Korolenko, TA., Ovsyukova, MV., Bgatova, NP., et al.[2022]

Trehalose, a sugar with pro-autophagy properties, significantly reduced eosinophilia and inflammation in a mouse model of eosinophilic chronic rhinosinusitis (ECRS) caused by autophagy deficiency in myeloid cells, indicating its potential as a therapeutic agent.

The anti-inflammatory effects of trehalose were found to be autophagy-independent and linked to reduced macrophage IL-1β production, with the sweet taste receptor T1R3 playing a crucial role in this mechanism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sweet taste receptor agonists attenuate macrophage IL-1β expression and eosinophilic inflammation linked to autophagy deficiency in myeloid cells. Lee, J., Kim, SJ., Choi, GE., et al.[2022]

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, a natural disaccharide, promotes cellular autophagy by inhibiting glucose transport through the SLC2A (GLUT) family of glucose transporters, which may help in treating diseases related to protein aggregation.

In animal studies, trehalose reduced liver fat (hepatic steatosis) and decreased lipid droplet accumulation in liver cells, suggesting its potential as a therapeutic agent for metabolic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trehalose inhibits solute carrier 2A (SLC2A) proteins to induce autophagy and prevent hepatic steatosis. DeBosch, BJ., Heitmeier, MR., Mayer, AL., et al.[2018]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10696978/

The effects of oral trehalose on glycaemia, inflammation, ...

Previous research has shown that 12-week trehalose ingestion improved glucose tolerance in subjects with BMI ≥ 23 kg/m2 and with a high risk for type 2 diabetes ...

2.

frontiersin.org

frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1580684/full

Assessing the efficacy of the natural disaccharide trehalose ...

Parenteral trehalose resulted in higher trehalose levels with lower serum glucose in Treh-KO mice, yet no additive metabolic benefits were observed. Overall, ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12171462/

Assessing the efficacy of the natural disaccharide trehalose ...

Our data also confirmed that i.p. trehalose treatment is therapeutically effective against weight gain and insulin insensitivity, but strikingly ...

4.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1756464619301379

Trehalose attenuates development of nonalcoholic ...

Trehalose intake markedly attenuates NASH manifestation in TSOD mouse. · Impaired glucose tolerance in TSOD mouse is also prevented by trehalose intake.

5.

nutritionj.biomedcentral.com

nutritionj.biomedcentral.com/articles/10.1186/s12937-020-00586-0

Daily consumption of one teaspoon of trehalose can help ...

Furthermore, we have demonstrated that daily consumption of 10 g of trehalose improves glucose tolerance in healthy humans [7], evaluated by ...

6.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S027869150200011X

Trehalose: a review of properties, history of use and human ...

No consistent treatment-related, dose-dependent adverse effects were observed in any of the eight safety studies performed at doses up to 10% of the diets. On ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S2451865424000711

Effect of trehalose on mortality and disease severity in ICU ...

The aim of this study is to assess the effectiveness of trehalose in improving clinical outcome and reducing mortality in ICU patients.

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7350577/

Daily consumption of one teaspoon of trehalose can help ...

Our findings suggest that trehalose helps lower postprandial blood glucose in healthy humans with higher postprandial glucose levels within the normal range.