Clinical trial NCT06930144: 5-MTHF Supplementation for Treatment of Type 1 Diabetes Patients
Official title: Immunomodulatory and Therapeutic Efficacy of 5-methyltetrahydrofolate Supplementation on Autoimmune Status in Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Shanghai Changzheng Hospital
Sponsor class: OTHER
First posted: 2025-04-16
Enrollment: 34
Sex: ALL
Minimum age (years): 13
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to evaluate the improvement of autoimmune status in patients with Type 1 Diabetes (T1D) through supplementation with 5-Methyltetrahydrofolate, and to explore the safety and efficacy of this treatment. The research seeks to provide new methods for the treatment of T1D and offer innovative ideas for enhancing the quality of life of T1D patients.


Eligibility criteria: Inclusion Criteria:

1. Diagnosed with T1D based on the World Health Organization (WHO) classification criteria for disease diagnosis.
2. Aged 13-65 years, regardless of gender.
3. Duration of T1D ≤ 5 years.
4. Retained residual islet function, defined as fasting C-peptide \> 0.1 nmol/L \[0.30 ng/mL\] or postprandial 2-hour C-peptide \> 0.2 nmol/L \[0.60 ng/mL\].
5. Determined by the investigator to be capable and willing to: perform self-monitoring of blood glucose (SMBG); complete patient logs as required; receive diabetes education; and comply with the study treatment and visit schedule as per the protocol.

6) Signed informed consent form, with parental/guardian consent and signature required for pediatric/adolescent participants.

Exclusion Criteria:

1. Serum 5-methyltetrahydrofolate or folate levels exceeding the upper limit of the normal reference range.
2. Currently experiencing acute metabolic disorders, such as diabetic ketoacidosis or hyperosmolar hyperglycemic state.
3. Women who are breastfeeding, pregnant, or planning to become pregnant during the trial.
4. Received immunosuppressive or immunomodulatory therapy within the past year.
5. Comorbid with other autoimmune diseases, such as systemic lupus erythematosus.
6. Severe liver, kidney, gastrointestinal, hematologic, cerebral, or circulatory system diseases.
7. Psychiatric or neurological disorders leading to non-cooperation, non-adherence to medication, substance abuse, or other related issues.
8. Malignancy.
9. Recent surgery or significant stress.
10. Known hypersensitivity or allergic reaction to 5-methyltetrahydrofolate or its excipients.
11. Investigator's judgment of significant evidence of severe, active, or uncontrolled endocrine or autoimmune abnormalities.
12. Currently participating in another clinical trial.

Primary outcomes:
measure: Islet β cell function
timeFrame: From enrollment to 24 weeks of treatment
Secondary outcomes:
measure: HbA1c
timeFrame: From enrollment to 24 weeks of treatment
measure: lymphocyte subsets
timeFrame: From enrollment to 24 weeks of treatment
measure: islet autoantibodies
timeFrame: From enrollment to 24 weeks of treatment
measure: insulin dosage
timeFrame: 24 weeks of treatment
measure: cytokines
timeFrame: From enrollment to 24 weeks of treatment
measure: CRP
timeFrame: From enrollment to 24 weeks of treatment
Other outcomes:
Locations:
Study officials:
References:
citation: Vukotic R, Di Donato R, Roncarati G, Simoni P, Renzulli M, Gitto S, Schepis F, Villa E, Berzigotti A, Bosch J, Andreone P. 5-MTHF enhances the portal pressure reduction achieved with propranolol in patients with cirrhosis: A randomized placebo-controlled trial. J Hepatol. 2023 Oct;79(4):977-988. doi: 10.1016/j.jhep.2023.06.017. Epub 2023 Jul 22.
citation: Verhaar MC, Wever RM, Kastelein JJ, van Dam T, Koomans HA, Rabelink TJ. 5-methyltetrahydrofolate, the active form of folic acid, restores endothelial function in familial hypercholesterolemia. Circulation. 1998 Jan 27;97(3):237-41. doi: 10.1161/01.cir.97.3.237.
citation: Giammarco S, Chiusolo P, Maggi R, Rossi M, Minnella G, Metafuni E, D'Alo F, Sica S. MTHFR polymorphisms and vitamin B12 deficiency: correlation between mthfr polymorphisms and clinical and laboratory findings. Ann Hematol. 2024 Oct;103(10):3973-3977. doi: 10.1007/s00277-024-05937-z. Epub 2024 Aug 28.