Efficacy and safety of taurine supplementation in A3243G-maternally-inherited diabetes and deafness

JRCT ID: jRCT2061190026

Registered date:24/12/2019

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: A3243G-maternally-inherited diabetes and deafness
• Date of first enrollment: 13/04/2020
• Target sample size: 40
• Study type: Interventional
• Intervention(s): After 3 months of the pre-observation period, the trail drugs, their daily doses specified by the weight category (taurine: 12 g for 40 kg or more, 9 g for less than 40 kg; placebo: comparator doses) will be orally administered 3 times a day after meals during 6 months of the observation period. The efficacy and safety of taurine for mitochondrial diabetes will be evaluated in comparison of placebo.

Outcome(s)

Primary Outcome

<Primary outcome>
HbA1c: change from baseline (before administration)

Secondary Outcome

<Important secondary outcomes>
(1) Daily dose of insulin: change from baseline (before administration)
(2) Daily dose of hypoglycemic drugs excluding insulin:
change from baseline (before administration)

<Secondary outcomes>
(1) HbA1c : change from baseline (before administration); in the patients whose HbA1c at registration is 7.0% or higher
(2) Insulin dosage : change from baseline (before
administration); in the patients whose HbA1c at registration is 7.0% or
higher
(3) Daily dose of hypoglycemic drug other than insulin: Change from baseline (before administration); in the patients
whose HbA1c at registration is 7.0% or higher
(4) Fasting blood glucose level: Change from baseline
(before administration)
(5) Achievement rate of less than 6%, 7%, 8% of HbA1c (at the end of administration: 24 weeks)
(6) Insulin secretion: [C peptide index (CPI) = CPR (ng / mL) / blood glucose (mg / dL) x100]
change from baseline (before administration)
(7) Fasting glucagon value: change from baseline (before
administration)
(8) Average hearing level (left / right: audiogram: quadrant B: change from baseline (before administration)
(9) Cardiac function: 12-lead ECG values + Echocardiogram value: change from baseline (before administration)
(10) Blood taurine level: change from baseline (before
administration)
(11) The taurine modification rate in the mitochondrial tRNALeu (UUR) in the peripheral blood leukocytes: change from
baseline (before administration)
(12) The mitochondrial ND6 protein level in the peripheral blood leukocytes: change from baseline (before
administration)
(13) The heteroplasmy (A3243G mutation rate) in the
peripheral blood leukocytes: change from baseline (before
administration)
(14) Blood lactate / pyruvate ratio: change from
baseline (before administration)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

After obtaining consent, at the time of registration, patients who meet all of the following inclusion criteria and have the ability to consent will be targeted in this trial :
(1) Diabetic patients harbouring 3243A>G point mutation proven to cause the taurine modification defect in the mitochondrial tRNALeu(UUR)
(2) Patients with HbA1c of 6.5% or more and less than 10.0% at the time of registration
(3) Patients over 20 years old when obtaining consent
(4) Patients who can be treated for diabetes through regular outpatient visits
(5) Patients with written consent from themseleves

Exclude criteria

Those who meet at least one of the following criteria will be excluded in this study :
(1) Patients who meet MELAS diagnostic criteria
(2) Patients who have started diabetes medication or changed diabetes treatment (used drugs, doses) during the pre-observation period or who have a plan to start or alter diabetes medication during the observation period
(3) Patients who have taken taurine within one year before registration
(4) Patients with the following serious systemic complications
Severe infection, status in pre- or post-surgery, or severe trauma
History of myocardial infarction, angina pectoris, or stroke
Severe renal dysfunction (eGFR<=30 mL / min / 1.73 m2)
Severe liver dysfunction (AST> 100 IU / L)
(5) Patients who are pregnant, breastfeeding or may be pregnant
(6) Patients with a history of hypersensitivity to taurine
(7) Patients with serious drug allergies such as anaphylactic shock or severe adverse events
(8) Patients who participated in other clinical trials and received a study drug within 12 weeks before obtaining consent
Patients who are judged to be ineligible for this study by investigator

Related Information

• Primary Sponsor: Sunada Yoshihide
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development