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

NCT ID: NCT04689971

Last Updated: 2020-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2/PHASE3

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-03

Study Completion Date

2021-11-30

Brief Summary

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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.

Detailed Description

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This was randomized clinical trial, active comparator, open label, controlled study from the period of November 2020 - November 2021 at Bethesda Hospital, Yogyakarta, Indonesia.

There were 60 painful diabetic neuropathy patients who fulfilled the inclusion and exclusion criteria. Each subject had been followed up from the first day of medication administration until 8 weeks after medication administration.

Ethical approval number ((kosong)) was obtained from Health Research Ethics Committee, Bethesda Hospital Yogyakarta.

The hypothesis of this study:

a. Add on oral vitamin B combination (B1, B6, and B12) to standard treatment in patients with painful diabetic neuropathy is more effective in reducing pain and neuropathic symptoms in 8 weeks of treatment compared with standard treatment, b. Add on oral vitamin B combination (B1, B6, and B12) to standard treatment in patients with painful diabetic neuropathy is as safe as standard treatment.

Conditions

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Painful Diabetic Neuropathy

Keywords

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Vitamin B combination B vitamins Standard therapy Diabetic neuropathy Neuropathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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).
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Open label

Study Groups

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Experimental Group

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).

Group Type EXPERIMENTAL

Standard therapy

Intervention Type DRUG

Gabapentin, pregabalin, or amitriptyline

Vitamin B combination

Intervention Type DRUG

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

Control Group

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

Group Type ACTIVE_COMPARATOR

Standard therapy

Intervention Type DRUG

Gabapentin, pregabalin, or amitriptyline

Interventions

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Standard therapy

Gabapentin, pregabalin, or amitriptyline

Intervention Type DRUG

Vitamin B combination

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

Intervention Type DRUG

Other Intervention Names

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Vitamin B complex

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* 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
Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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PT SOHO Global Health Tbk

UNKNOWN

Sponsor Role collaborator

Duta Wacana Christian University

OTHER

Sponsor Role lead

Responsible Party

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Rizaldy Taslim Pinzon

Principal investigator, Neurologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Rizaldy Pinzon, MD, MSc, PhD

Role: PRINCIPAL_INVESTIGATOR

Duta Wacana Christian University

Locations

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Bethesda Hospital Yogyakarta

Yogyakarta, Special Region of Yogyakarta, Indonesia

Site Status RECRUITING

Countries

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Indonesia

Central Contacts

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Rizaldy T Pinzon, MD, MSc, PhD

Role: CONTACT

Phone: +62 81294638229

Email: [email protected]

Vanessa Veronica, BM

Role: CONTACT

Phone: +62 89605559529

Email: [email protected]

Facility Contacts

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Rizaldy T Pinzon, MD, MSc, PhD

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 15289425 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 17176168 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26892473 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 16495296 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24835269 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20045411 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31624024 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16008162 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23970715 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17030830 (View on PubMed)

Other Identifiers

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SOHOBION

Identifier Type: -

Identifier Source: org_study_id