NCT04711980

Brief Summary

Background: Diabetic peripheral neuropathy (DPN) is a common and disabling chronic microvascular complications in patients with type 2 diabetic Mellitus (T2DM) that is characterized by nerve damage, affecting at least half of patients diagnosed with diabetes. It has been reported that DPN significantly contributes to the increased morbidity with diabetic foot ulcers by 60% and amputation by 85% that seriously threaten the quality of life. Mudan granule, a traditional Chinese medicinal preparation, is widely used in clinical practice for DPN in China. Evidence from clinical and preclinical studies have shown that Mudan granule could relieve symptoms and reduce the incidence of DPN exacerbations. However, the previous studies are of variable quality and poorly standardized,which limits the clinical application of Mudan granule. This study evaluates the efficacy and safety of Mudan granule combined with methylcobalamin in the treatment of type 2 diabetic peripheral neuropathy, providing the highest level of evidence of Mudan granule. Methods and design: A randomized, double-blind, placebo-controlled,parallel-arm, and multi-centric clinical trial design was used based on a co-regimen of methylcobalamin. Subjects who met the inclusion criteria were randomly divided into two groups. The patients in the study group were treated with Mudan granule combined with methylcobalamin, and the patients in the control group were treated with placebo combined with methylcobalamin. The total intervention period is 24 weeks. The sample size was 402 cases. Major evaluation indicators: Michigan Diabetic Neuropathy Score (MDNS) changes, the changes of MDNS were compared between the two groups before and after medication, adopting the evaluation method of difference values. Secondary Evaluation Indicators:(1) nerve conduction velocity changes, the changes in nerve conduction velocity of each nerve were compared between the two groups before and after taking medicine, adopting the evaluation method of difference values. (2)corneal nerve fiber density changes, the changes in corneal nerve fiber density of each mm2 were compared between the two groups before and after taking medicine, adopting the evaluation method of difference values. (3)corneal nerve branch density changes, the changes in corneal nerve branch density of each mm2 were compared between the two groups before and after taking medicine, adopting the evaluation method of difference values. (4)corneal nerve fiber length changes, the changes in corneal nerve fiber length of each mm2 were compared between the two groups before and after taking medicine, adopting the evaluation method of difference values. (5)Toronto Clinical Scoring System (TCSS) changes, the changes of toronto clinical score were compared between the two groups before and after taking medicine, adopting the evaluation method of difference values. (6)Traditional Chinese Medicine(TCM) syndromes efficacy score changes, the changes in TCM syndromes efficacy score were compared between the two groups before and after taking medicine, adopting the evaluation method of difference values. (7) Clinical symptoms score changes, the changes of each of clinical symptoms score were compared between the two groups before and after medication, adopting the evaluation method of difference values. Discussion: We postulate that patients with type 2 diabetic peripheral neuropathy will benefit from therapy with Mudan granule.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
402

participants targeted

Target at P75+ for early_phase_1

Timeline
Completed

Started Jun 2021

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 7, 2021

Completed
8 days until next milestone

First Posted

Study publicly available on registry

January 15, 2021

Completed
5 months until next milestone

Study Start

First participant enrolled

June 1, 2021

Completed
8 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2022

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2022

Completed
Last Updated

January 15, 2021

Status Verified

January 1, 2021

Enrollment Period

8 months

First QC Date

January 7, 2021

Last Update Submit

January 13, 2021

Conditions

Diabetic Peripheral Neuropathy Type 2

Keywords

Type 2 Diabetes Mellitusdiabetic peripheral neuropathyMudan granule

Outcome Measures

Primary Outcomes (1)

  • Changes in total score on the Michigan Diabetic Neuropathy Score (MDNS) of Scale

    MDNS was recorded on the Michigan Diabetic Neuropathy Score of Scale. The changes of MDNS were compared between the two groups before and after medication, adopting the evaluation method of difference values. The total score was 46, ranging from 0 (least severe) to 46 (most severe).

    0,12,24 weeks

Secondary Outcomes (7)

  • Changes in nerve conduction velocity

    (0,24 weeks)

  • Changes in corneal nerve fiber density of each mm2

    (0,24 weeks)

  • Changes in corneal nerve branch density of each mm2

    (0,24 weeks)

  • Changes in corneal nerve fiber length of each mm2

    (0,24 weeks)

  • Changes in total score on the Toronto Clinical Scoring System (TCSS) of Scale

    (0,12,24 weeks)

  • +2 more secondary outcomes

Study Arms (2)

Mudan granule

EXPERIMENTAL

Based on the standard medical care, experimental group were treated with Mudan Granule 7g , 3 times/d. Intervention: Drug: Mudan granule

Drug: Mudan granule

Placebo

PLACEBO COMPARATOR

Based on the standard medical care, placebo-controlled group were treated with Placebo 7g , 3 times/d Intervention: Drug: Placebo

Drug: Placebo

Interventions

Mudan granuleDRUG

Mudan granule,a traditional Chinese medicine formula,consists of nine Chinese herbs. Other: Standard medical care.Standard medical care is in accordance with China Guideline for type 2 diabetes (2013).

Also known as: Mudan particle
Mudan granule
PlaceboDRUG

Granule(Placebo) is in accordance with Mudan granule in appearance, colour, taste. Other: Standard medical care. Standard medical care is in accordance with China Guideline for type 2 diabetes (2013).

Also known as: Placebos
Placebo

Eligibility Criteria

Age30 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Meet the diagnostic criteria of type 2 diabetic peripheral neuropathy.
  • Meet the diagnostic criteria of TCM syndrome differentiation of qi deficiency and collaterals obstruction.
  • The patient's age is between 30-70 years.
  • At least 2 nerve conduction velocities have decreased on electromyography.
  • Sign informed consent.

You may not qualify if:

  • Recent use of antioxidants such as vitamin E or vitamin C, acute infection, liver and kidney dysfunction, acute complications of diabetes, severe cardiovascular and cerebrovascular diseases,neuropathy caused by long-term alcohol consumption and other factors.
  • Besides methylcobalamin,the drugs such as alpha lipoic acid, epalrestat, VitB12, Chinese patent medicine and decoction have been used to treat diabetic peripheral neuropathy within 4 weeks before enrollment.
  • Systolic blood pressure \> 160 millimeters of mercury (mmHg) or diastolic blood pressure \> 100mmHg.
  • Having the diabetic ketoacidosis, ketoacidosis and severe infection within one month.
  • Combined with cardiovascular, liver, kidney and hematopoietic system and other serious primary disease, serum transaminase beyond the normal value more than 2 times, serum creatinine greater than the upper limit of normal, psychiatric patients.
  • Pregnancy, prepared to pregnant or lactating women.
  • Having a history of multiple drug allergies or being allergic to the ingredients of Mudan granule.
  • Participate in other clinical studies within one month.
  • Drinking alcohol excessive and/or taking psychoactive substances, drug abusers and dependents over the past five years.
  • Having a history of active ophthalmopathy,ocular surgery,glaucoma,acute and chronic corneal diseases,extended-wearing contact lens and so on.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Guang'anmen Hospital of China Academy of Chinese Medical Sciences

Beijing, China

Location

Related Publications (1)

  • Zhang Y, Jin D, Duan Y, Hao R, Chen K, Yu T, Lian F, Tong X. Efficacy of Mudan Granule (Combined With Methylcobalamin) on Type 2 Diabetic Peripheral Neuropathy: Study Protocol for a Double-Blind, Randomized, Placebo-Controlled, Parallel-Arm, Multi-Center Trial. Front Pharmacol. 2021 May 20;12:676503. doi: 10.3389/fphar.2021.676503. eCollection 2021.

    PMID: 34093204DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Study Officials

  • Xin hua Xiao, Ph.D.

    Peking Union Medical College Hospital

    PRINCIPAL INVESTIGATOR

  • Yi Li, Ph.D.

    Beijing Hospital

    PRINCIPAL INVESTIGATOR

  • Shi jia Yu, Ph.D.

    Affiliated Hospital of Liaoning University of Traditional Chinese Medicine

    PRINCIPAL INVESTIGATOR

  • Yan gang Wang, Ph.D.

    The Affiliated Hospital of Qingdao University

    PRINCIPAL INVESTIGATOR

  • Qiu Chen, Ph.D.

    Chengdu University of Traditional Chinese Medicine

    PRINCIPAL INVESTIGATOR

  • Wu quan Deng, Ph.D.

    The Fourth People's Hospital of Chongqing

    PRINCIPAL INVESTIGATOR

  • Zhi gang Zhao, Ph.D.

    Zhengzhou Yihe Hospital Affiliated to Henan University

    PRINCIPAL INVESTIGATOR

  • Zhen qiang Song, Ph.D.

    Zhu Xianyi Memorial Hospital of Tianjin Medical University

    PRINCIPAL INVESTIGATOR

  • Ping Liu, Master

    The Third Hospital of Xi'an

    PRINCIPAL INVESTIGATOR

  • Yi ming Li, Ph.D.

    Huashan Hospital

    PRINCIPAL INVESTIGATOR

  • Jing Liu, Ph.D.

    Gansu Provincial People's Hospital

    PRINCIPAL INVESTIGATOR

  • Chun Li Piao, Ph.D.

    Shenzhen Hospital of Guangzhou University of Traditional Chinese Medicine

    PRINCIPAL INVESTIGATOR

  • Xiu ge Wang, Master

    Affiliated Hospital of Changchun University of Chinese Medicine

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Feng mei Lian, Ph.D.

CONTACT

0086-010-88001402237440782@qq.com

Yue hong Zhang, Master

CONTACT

18600867272zyhong2835@sina.com

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
chief physician, Professor, endocrinology department of Guang'anmen Hospital of China Academy of Chinese Medical Sciences

Study Record Dates

First Submitted

January 7, 2021

First Posted

January 15, 2021

Study Start

June 1, 2021

Primary Completion

February 1, 2022

Study Completion

September 1, 2022

Last Updated

January 15, 2021

Record last verified: 2021-01

Locations

CN(1)