The Benefits of Vitamin B Combination as Add on Therapy in the Management of Painful Diabetic Neuropathy Patient

NCT04689971 | Unknown Phase 2

• 1 other identifier: SOHOBION
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Large population-based study has shown that the prevalence of painful diabetic neuropathy (PDN) is around 21%, and painful symptoms are more prevalent in patients with type 2 diabetes, females, and Asians. PDN is characterized by symmetrical lower limb paresthesiae, dysesthesiae, lancinating pains and allodynia, with nocturnal exacerbation. PDN cause sleep disturbance and reduce quality of life. The international guidelines advocate a range of therapies for symptom relief. The therapeutic efficacy for all recommended medications is at best around 50% pain relief and is limited due to unwanted side effects. Apart from peripheral and central alterations, metabolic alterations such as increased glycemic influx, and elevated plasma methylglyoxal levels have been implicated in the pathogenesis of PDN. Several treatment options for PN are available, including pharmacological, non-pharmacological, and alternative options. Patients suffering from severe and disabling symptoms (e.g. NeP) may require guideline treatments like pregabalin, duloxetine, or gabapentin initially until the symptoms are under control. These medications can symptomatically relieve NeP; however, they do not address the underlying cause. Other options such as neurotropic B vitamins (B1, B6, and B12) do not only target the symptoms, but also improve nerve health and contribute to nerve regeneration. The B vitamins are commonly used for PN treatment in clinical practice worldwide, this treatment option is most suitable before the patient suffers from chronic NeP. However, co-treatment with neurotropic B vitamins is also appropriate in NeP patients, to ensure the restoration of nerve health.

Conditions

Painful Diabetic Neuropathy

Keywords

Vitamin B combination; B vitamins; Standard therapy; Diabetic neuropathy; Neuropathy

Outcome Measures

Primary Outcomes (6)

• Improvement in Visual Analogue Scale (VAS) at week 4

  Change in pain impact on daily life as measured by Visual Analogue Scale (VAS) from its baseline value. Visual analogue scale is a continuous scale comprised of a horizontal or vertical line, usually 10 centimeters (100 mm) in length, anchored by 2 verbal descriptors, one for each symptom extreme. The scale is most commonly anchored by "no pain" (score of 0) and "pain as bad as it could be" or "worst imaginable pain" (score of 100). The respondent is asked to place a line perpendicular to the VAS line at the point that represents their pain intensity. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the "no pain" anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity.

  4 weeks after treatment initiation

• Improvement in Visual Analogue Scale (VAS) at week 8

  Change in pain impact on daily life as measured by Visual Analogue Scale (VAS) from its baseline and week 4 value. Visual analogue scale is a continuous scale comprised of a horizontal or vertical line, usually 10 centimeters (100 mm) in length, anchored by 2 verbal descriptors, one for each symptom extreme. The scale is most commonly anchored by "no pain" (score of 0) and "pain as bad as it could be" or "worst imaginable pain" (score of 100). The respondent is asked to place a line perpendicular to the VAS line at the point that represents their pain intensity. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the "no pain" anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity.

  8 weeks after treatment initiation

• Improvement in Numeric Pain Scale at week 4

  Change in pain impact on daily life as measured by Numeric Pain Scale from its baseline value. Numeric pain scale is a segmented numeric version of the visual analog scale (VAS) in which a respondent selects a whole number (0-10 integers) that best reflects the intensity of his/her pain. Higher scores indicating greater pain intensity.

  4 weeks after treatment initiation

• Improvement in Numeric Pain Scale at week 8

  Change in pain impact on daily life as measured by Numeric Pain Scale from its baseline and week 4 value. Numeric pain scale is a segmented numeric version of the visual analog scale (VAS) in which a respondent selects a whole number (0-10 integers) that best reflects the intensity of his/her pain. Higher scores indicating greater pain intensity.

  8 weeks after treatment initiation

• Improvement in Brief Pain inventory at week 4

  Change in pain impact on daily life as measured by Brief Pain Inventory from its baseline value. The Brief Pain Inventory evaluates a patient's pain experience through a number of different scales. There are line drawings of the front and back of a human body on which patients mark the location of their pain. Patients are asked to list the treatments or medications that they are using and how much relief they have provided in the past 24 hours. In addition, patients fill out 11 different numeric rating scale that ask about pain intensity (ranging from 0 to 10) and the effect of the pain on their ability to function during various activities of daily living. A higher score indicates greater pain intensity.

  4 weeks after treatment initiation

• Improvement in Brief Pain inventory at week 8

  Change in physician global assessment from its baseline value. The Brief Pain Inventory evaluates a patient's pain experience through a number of different scales. There are line drawings of the front and back of a human body on which patients mark the location of their pain. Patients are asked to list the treatments or medications that they are using and how much relief they have provided in the past 24 hours. In addition, patients fill out 11 different numeric rating scale that ask about pain intensity (ranging from 0 to 10) and the effect of the pain on their ability to function during various activities of daily living. A higher score indicates greater pain intensity.

  8 weeks after treatment initiation

Study Arms (2)

Experimental Group

EXPERIMENTAL

Receive standard therapy consists of gabapentin, pregabalin, or amitriptyline and vitamin B combination (B1 100 mg, B2 200 mg and B12 200 mcg) tablet once daily (experimental group).

Drug: Standard therapy; Drug: Vitamin B combination

Control Group

ACTIVE COMPARATOR

Receive standard therapy consists of gabapentin, pregabalin, or amitriptyline.

Drug: Standard therapy

Interventions

Standard therapy DRUG

Gabapentin, pregabalin, or amitriptyline

Control Group; Experimental Group

Vitamin B combination DRUG

Vitamin B combination (B1 100 mg, B2 200 mg and B12 200 mcg) tablet once daily

Also known as: Vitamin B complex

Experimental Group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female
• Adult age (\>18 years old)
• Diagnosed as painful diabetic neuropathy based on validated Diabetic Neuropathy Symptoms (DNS) and Diabetic Neuropathy Examination (DNE)

You may not qualify if:

• Subjects with significant renal and liver problem
• Subjects with known hypersensitivity to vitamin B combination
• Pregnancy and breastfeeding patients
• Patients that enrolled any clinical trial within a month
• Not competent enough in giving approval and answering questionnaires

Sponsors & Collaborators

• Duta Wacana Christian University: lead
• PT SOHO Global Health Tbk: collaborator

Study Sites (1)

Bethesda Hospital Yogyakarta

Yogyakarta, Special Region of Yogyakarta, 55224, Indonesia

RECRUITING

Related Publications (10)

• Andres E, Loukili NH, Noel E, Kaltenbach G, Abdelgheni MB, Perrin AE, Noblet-Dick M, Maloisel F, Schlienger JL, Blickle JF. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ. 2004 Aug 3;171(3):251-9. doi: 10.1503/cmaj.1031155.

  PMID: 15289425 BACKGROUND

• Head KA. Peripheral neuropathy: pathogenic mechanisms and alternative therapies. Altern Med Rev. 2006 Dec;11(4):294-329.

  PMID: 17176168 BACKGROUND

• Jayabalan B, Low LL. Vitamin B supplementation for diabetic peripheral neuropathy. Singapore Med J. 2016 Feb;57(2):55-9. doi: 10.11622/smedj.2016027.

  PMID: 26892473 BACKGROUND

• Liu KW, Dai LK, Jean W. Metformin-related vitamin B12 deficiency. Age Ageing. 2006 Mar;35(2):200-1. doi: 10.1093/ageing/afj042.

  PMID: 16495296 BACKGROUND

• Negrao L, Almeida P, Alcino S, Duro H, Liborio T, Melo Silva U, Figueira R, Goncalves S, Neto Parra L. Effect of the combination of uridine nucleotides, folic acid and vitamin B12 on the clinical expression of peripheral neuropathies. Pain Manag. 2014 May;4(3):191-6. doi: 10.2217/pmt.14.10. Epub 2014 May 16.

  PMID: 24835269 BACKGROUND

• Okada K, Tanaka H, Temporin K, Okamoto M, Kuroda Y, Moritomo H, Murase T, Yoshikawa H. Methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle and promotes nerve regeneration in a rat sciatic nerve injury model. Exp Neurol. 2010 Apr;222(2):191-203. doi: 10.1016/j.expneurol.2009.12.017. Epub 2010 Jan 4.

  PMID: 20045411 BACKGROUND

• Selvarajah D, Kar D, Khunti K, Davies MJ, Scott AR, Walker J, Tesfaye S. Diabetic peripheral neuropathy: advances in diagnosis and strategies for screening and early intervention. Lancet Diabetes Endocrinol. 2019 Dec;7(12):938-948. doi: 10.1016/S2213-8587(19)30081-6. Epub 2019 Oct 14.

  PMID: 31624024 BACKGROUND

• Sun Y, Lai MS, Lu CJ. Effectiveness of vitamin B12 on diabetic neuropathy: systematic review of clinical controlled trials. Acta Neurol Taiwan. 2005 Jun;14(2):48-54.

  PMID: 16008162 BACKGROUND

• Tesfaye S, Boulton AJ, Dickenson AH. Mechanisms and management of diabetic painful distal symmetrical polyneuropathy. Diabetes Care. 2013 Sep;36(9):2456-65. doi: 10.2337/dc12-1964.

  PMID: 23970715 BACKGROUND

• Ting RZ, Szeto CC, Chan MH, Ma KK, Chow KM. Risk factors of vitamin B(12) deficiency in patients receiving metformin. Arch Intern Med. 2006 Oct 9;166(18):1975-9. doi: 10.1001/archinte.166.18.1975.

  PMID: 17030830 BACKGROUND

MeSH Terms

Conditions

Diabetic Neuropathies

Interventions

Standard of Care; cyanocobalamin, pyridoxine, thiamine drug combination; Vitamin B Complex

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Vitamins; Micronutrients; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Rizaldy Pinzon, MD, MSc, PhD

  Duta Wacana Christian University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rizaldy T Pinzon, MD, MSc, PhD

CONTACT

+62 81294638229; drpinzon17@gmail.com

Vanessa Veronica, BM

CONTACT

+62 89605559529; vanessaveronica73@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator, Neurologist

Model Details: Eligible subjects were randomly allocated to receive any of the following regiments: standard therapy consists of pregabalin, gabapentine, or amitriptyline (control group) or standard therapy and vitamin B combination (vitamin B1 100 mg, B6 200 mg and B12 200 mcg) tablet once daily (experimental group).

Study Record Dates

• First Submitted: December 19, 2020
• First Posted: December 30, 2020
• Study Start: November 3, 2020
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2021
• Last Updated: December 30, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)