Clinical trial NCT06568185: The Effect of Alpha Lipoid Acid and Vitamin B Preparation on Diabetic Polyneuropathy in Type 2 Diabetes Mellitus Patient
Official title: The Effectiveness of Fixed Dose Combination of Alpha Lipoic Acid and Vitamin B Preparations for Treatment of Diabetic Polyneuropathy in Type 2 Diabetes Mellitus Patients: A Randomized Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diabetic Polyneuropathy
Lead sponsor: Universiti Sains Malaysia
Sponsor class: OTHER
Collaborators: name: BREGO Life Sciences Sdn Bhd
First posted: 2024-08-23
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The participants then will be randomized to either intervention or control group. The intervention group will receive a fixed dose combination of alpha lipoic acid and vitamin B preparations, and the control group will receive a placebo (look-alike substance that contains no drug).
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy of combination of vitamin B and alpha lipoic acid formulations for the treatment of diabetic polyneuropathy in individuals with type 2 diabetes mellitus.

Methodology :

This is a single-center, randomized, double-blind, placebo-controlled trial study.

Study duration May 2024 - September 2025

Study location :

This study will be conducted at the Klinik Rawatan Keluarga and diabetes clinic Hospital Universiti Sains Malaysia.

Source Reference :

People with type 2 diabetes mellitus attending the Hospital Universiti Sains Malaysia.

Study source population :

People with type 2 diabetes mellitus attended Klinik Rawatan Keluarga and diabetes clinic Hospital Universiti Sains Malaysia during the study period.

Detailed description: General objective

To determine the effectiveness of a fixed dose combination of alpha lipoic acid and vitamin B preparations in comparison with incative drug for treatment of diabetic polyneuropathy (DPN) in people with type 2 diabetes mellitus.

Research hypothesis

1. There are significant improvements in mean total symptom score (TSS) and neuropathic symptoms score (NSS) in people with diabetic polyneuropathy taking a fixed dose combination of alpha lipoic acid and vitamin B preparations as compared to diabetic polyneuropathy patients taking a placebo.
2. There are significant improvements in total symptom score (TSS) and neuropathic symptoms score (NSS) among people with diabetic polyneuropathy taking a fixed dose combination of alpha lipoic acid and vitamin B preparations for 12 weeks.
3. There are significant improvements in fasting plasma glucose, HbA1C level, fasting lipid profile, body mass index (BMI), and diabetes quality of life in people with diabetes taking a fixed dose combination of alpha lipoic acid and vitamin B preparations as compared to diabetic patients taking placebo.
4. There are no significant differences in the safety parameters of renal function and liver function tests among people with diabetic polyneuropathy at baseline and 12 weeks after taking a fixed dose combination of alpha lipoic acid and vitamin B preparations.
5. There are significant improvements in fasting plasma glucose, HbA1C level, fasting lipid profile, body mass index (BMI), and diabetes quality of life among diabetic patients taking a fixed dose combination of alpha lipoic acid and vitamin B preparations for 12 weeks.

Method of data collection

This study will be conducted after obtaining approval from the Universiti Sains Malaysia Ethical Committee (JPeM) and will be conducted in accordance to World Medical Association Declaration of Helsinki ethical principles for medical research involving human subjects.

Recruitment of subject

Participants will be recruited from Klinik Rawatan Keluarga and diabetes clinic Hospital USM via convenience sampling. Potential participants will be identified from the case notes of patients. Then, the participants will be approached individually. Those who are willing to participate in this study will be given information regarding the study. The participants will be screened to determine their eligibility criteria, including performing neurological symptom score (NSS) and neuropathy disability score (NDS) to determine diabetes polyneuropathy diagnosis. If all the inclusion and exclusion criteria are fulfilled, informed consent will be obtained from all patients who agree to participate in this study. The consent will be obtained by a study team that recruited the patient. Upon consented, the participant's socio-demographic data will be collected, and the medical record will be assessed to fill in their medical and diabetes profiles. They will also answer the total symptoms score (TSS), and revised version of the Diabetes Quality of Life (Rv-DQoL) questionnaire. The physical examination includes measurement of height, weight, calculated Body Mass Index (BMI), and blood pressure during sitting will be done. Then 6ml of fasting venous blood will be taken for measurement of HbA1c, fasting blood glucose, renal function test, liver function test and fasting lipid profile as baseline. All participants were advised not to consume any special supplement or other replacement meal throughout the study.

The participants then will be randomized to either intervention or control group. The intervention group will receive a fixed dose combination of alpha lipoic acid and vitamin B preparations, and the control group will receive a placebo (look-alike substance that contains no drug).

The participants will be seen 6 weeks after taking the product. During this visit, they will be assessed for any side effects or adverse events and compliance with the product supplied (compliance form). The total symptoms score (TSS), neurological symptom score (NSS), a revised version of Diabetes Quality of Life (Rv-DQoL), blood pressure, weight, height, calculated Body Mass Index (BMI) will also be measured. Another 6-week supply of the product will be given.

Lastly, the participants will be assessed in week 12. During this visit, the same measurement will be taken as visit 1, including answering the questionnaires. Adverse events, blood taking, and compliance will also be assessed.

The duration for visit 1 and visit 3 (at 12 weeks) is about 50-60 minutes for each visit since it will involve blood taking procedure. Duration for visit 2 (at 6 weeks) is about 30 minutes since it will not involve blood taking.

Intervention group: Fixed dose combination of alpha lipoic acid and vitamin B preparations

At baseline, the intervention group will receive a fixed dose combination of alpha lipoic acid and vitamin B preparations. This product is packaged and manufactured by BREGO Life Sciences Sdn Bhd company with a brand name of Bionerv®. BIONERV® is the first combination of alpha lipoic acid 300mg and vitamin B complex. Bionerv® is in oral film-coated, orange colour, oblong shape and no marking and embossing on the tablet. Each tablet contains 4 active ingredients as follows: Alpha lipoic acid 300mg, Vitamin B12 (methylcobalamin) 500mcg, Vitamin B6 (pyridoxine) 8mg, Vitamin B1 (thiamine) 39mg. All the above ingredients are synthetic. The shelf-life is 2 years. Storage condition is keeping in dry place below 300oC and protecting from light and moisture. It has no bovine-gelatin capsule. There are no precautions on drug-drug interaction, but it is not suitable for children (\<18 years). There is insufficient reliable data for pregnancy and breast feeding. One bottle consists of 60 tablets.

This medication needs to take 2 tablets a day after a meal and need to drink more water. In this study, the participants need to take 2 tablets once daily after breakfast. The duration of the intervention will be 12 weeks. All participants are required to return to the clinic in the 6th and 12th week for a post-intervention assessment.

Control group

At baseline, the control group will receive a placebo drug consisting of Croscamellose Sodium, Microcrystalline Cellulose, Silicon Dioxide and Magnesium stearate. The placebo was manufactured by Yanling Natural Hygiene Sdn Bhd. The formulation of the placebo tablet is derived from the excipients used in the Bionerv tablet.

The participants need to take 2 tablets once daily after breakfast. The placebo drugs will share the same appearance and color as intervention drug.

The duration of the intervention will be 12 weeks. All participants are required to return to the clinic in the 6th and 12th week for a post-intervention assessment.

Follow up

There are two follow-ups during this study. 1st follow-up will be on the 6th week and 2nd follow-up (final follow-up) will be during 12th week of the study.

During the 6th week follow-up, participants will be checked for their weight, height, calculated Body Mass Index (BMI), TSS, NSS, RV-DQoL questionnaire, compliance, and adverse effects.

A final visit (12th week) to the clinic will be conducted on the 12th week. During these visits, the outcome measures will be assessed to determine the effect of the fixed-dose combination of alpha lipoic acid and vitamin B. During this visit, the same measurement will be taken as visit 1.

Eligibility criteria: Inclusion Criteria:

1. Aged 18 years and over
2. Diagnosed with type 2 diabetes mellitus based on WHO diagnostic criteria for diabetes (Organization, 2020).
3. Diagnose with diabetic polyneuropathy by Neurological Symptom Score (NSS) and Neuropathy Disability Score (NDS).

Exclusion Criteria:

1. Those with a documented mental impairment which impacted on their ability to answer questions independently.
2. People with peripheral vascular disease (non-palpable foot pulses, intermittent claudication)
3. People with an amputated foot or leg
4. Abnormal liver enzyme.
5. People with renal impairment.
6. People using drugs with possible influence on the study results (antidepressants, anticonvulsants, opiates, neuroleptics, antioxidants, and particularly methylcobalamin, pyridoxine and other B complex preparations)
7. Pregnancy, lactation, or childbearing age without safe contraception
8. History of allergy with vitamin B complex preparations (i.e. Vitamin B12, B6 and B1) and alpha lipoic acid.

Primary outcomes:
measure: To compare the mean change in Total symptom score (TSS) over 12 a week period
timeFrame: baseline, 6 weeks and 3 month
measure: To compare the mean change in Neuropathic symptoms score (NSS) over 12 a week period
timeFrame: baseline, 6 weeks and 3 month
Secondary outcomes:
measure: compare the changes in the fasting plasma glucose over 12 a week period
timeFrame: baseline and 3 month
measure: compare the changes in the fasting lipid profile over 12 a week period
timeFrame: baseline and 3 month
measure: compare the changes in the HbAIC level over 12 a week period
timeFrame: baseline and 3 month
measure: compare the changes in blood pressure over 12 a week period
timeFrame: baseline and 3 month
measure: compare the changes in diabetes quality of life over 12 a week period
timeFrame: baseline, 6 weeks and 3 month
measure: compare the differences in the safety parameters of renal function
timeFrame: baseline and 3 month
measure: compare the differences in the safety parameters of liver function
timeFrame: baseline and 3 month
measure: compare the changes in participant weight.
timeFrame: baseline, 6 weeks and 3 month
measure: participant height.
timeFrame: baseline
measure: compare the changes in participant Body Mass Index (BMI)
timeFrame: baseline, 6 weeks and 3 month
Other outcomes:
Locations:
city: Kubang Kerian
country: Malaysia
facility: Hospital Universiti Sains Malaysia
state: Kelantan
Study officials:
affiliation: Department of Family Medicine, School of Medical Sciences University Sains Malaysia, Health Campus
name: Che Nur Ain Che Abdullah, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Family Medicine, School of Medical Sciences University Sains Malaysia, Health Campus
name: Noraini Mohamad, Dr.
role: STUDY_DIRECTOR
affiliation: Department of Family Medicine, School of Medical Sciences University Sains Malaysia, Health Campus
name: Nani Draman, Prof. Dr.
role: STUDY_CHAIR
affiliation: Department of Family Medicine, School of Medical Sciences University Sains Malaysia, Health Campus
name: Ritzzaleena Rosli Mohd Rosli, Dr.
role: STUDY_CHAIR
affiliation: Department of Family Medicine, School of Medical Sciences University Sains Malaysia, Health Campus
name: Zainab Mat Yudin@Badrin, Dr.
role: STUDY_CHAIR
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