Buyuan-zhixiao Formula in the Treatment of Elderly Patients With Diabetes and Multiple Metabolic Disorders

Clinical Research on Evidence Based Traditional Chinese Medicine for Elderly Diabetes Based on State Target Theory-Buyuan Zhixiao Fang in the Treatment of Elderly Patients With Diabetes and Multiple Metabolic Disorders: Study Protocol for a Multicenter, Randomized, Double-blind, Placebo-controlled Trial

The primary objective of this clinical trial is to assess the clinical efficacy and safety of the Buyuan Zhixiao Formula in treating elderly patients with diabetes and multiple metabolic disorders exhibiting symptoms of renal deficiency and blood stasis. Furthermore, this study aims to intervene in high-risk factors to prevent arteriosclerosis and to investigate the clinical efficacy of the Buyuan Zhixiao Formula in the prevention and treatment of cognitive impairments.

The main questions it aims to answer are:

1. What are the clinical effects of Buyuan Zhixiao Formula, including lowering blood sugar, lowering blood pressure, lowering lipids, and treating obesity?
2. Can Buyuan Zhixiao Formula improve cognitive impairment in diabetes? Researchers compared Buyuan Zhixiao Formula with a placebo (a drug that looks similar but contains only 10% of the active ingredients) to see if the drug Buyuan Zhixiao Formula can treat elderly people with diabetes and multiple metabolic disorders.

Participants will:

1. Take the drug Bu Yuan Zhi XiaoFormula or placebo every day for 6 months；Follow-up for 6 months；
2. Check fasting blood sugar and 2-hour postprandial blood sugar every month; check HbA1c, blood lipids, vascular function, and cognitive impairment serum markers every 3 months;
3. Conduct scores on TCM symptoms, cognitive ability, nutritional status and other scales and adverse events;
4. Urine and serum samples were collected before and after treatment;

Study Overview

• Status: Not yet recruiting
• Conditions: Aging; Diabete Mellitus; Randomized Controlled Trial; Metabolic Disorders; Traditional Chinese Medicine
• Intervention / Treatment: Drug: Buyuan Zhixiao Formula; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Qing Ni, postgraduate; Phone Number: 13701253942; Email: 1831479145@qq.com
• Study Contact Backup: Name: zhige Wen, postgraduate; Phone Number: 15890643963; Email: 1831479145@qq.com

Study Locations

• China
  • Hebei, China
    • Cangzhou integrative medicine hospital
    • Contact: zhongyong zhang, postgraduate; Phone Number: 18031783396; Email: zzyhappy666@126.com
  • Neimeng, China
    • Hohhot Mongolian Traditional Chinese Medicine Hospital
  • Shandong, China
    • Binzhou Traditional Chinese Medicine Hospital
    • Contact: lijuan Du, postgraduate; Phone Number: 18800102622; Email: 137425497@qq.com
  • Shandong, China
    • Yantai Baishi Traditional Chinese Medicine Hospital
  • Tianjin, China
    • The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine
    • Contact: bin Wang, postgraduate; Phone Number: 13051395068
  • Beijing
    • Beijin, Beijing, China, 100053
      • China Academy of Chinese Medical Sciences Guang'anmen Hospital
      • Contact: zhige Wen, postgraduate; Phone Number: 15890643963; Email: 1831479145@qq.com
      • Contact: Qing Ni, postgraduate; Phone Number: 010-88001245; Email: 1831479145@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1.Age ≥65 years, irrespective of sex;
• 2.Individuals who meet the Western medical diagnostic criteria for type 2 diabetes mellitus (T2DM) in the elderly, with a hemoglobin A1c level of ≥7.0% in the past three months;
• 3.Compliance with the diagnostic criteria for abdominal obesity (waist circumference ≥90 cm for males and ≥85 cm for females);
• 4.Conformity to the diagnostic standards for hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg);
• 5.A history of dyslipidemia, where lipid levels have not reached the general control standards for elderly individuals with T2DM following oral lipid-lowering therapy (statins/bile acid sequestrants): LDL cholesterol <2.6 mmol/L and/or triglycerides <2.5 mmol/L;
• 6.Diagnosis of kidney deficiency and blood stasis according to traditional Chinese medicine, with the pattern type referring to the《Guidelines for Clinical Research of New Chinese Medicines》;
• 7.Willingness to sign an informed consent document.

Exclusion Criteria:

• 1.Exclusion of individuals who, within the past week, have experienced severe infections, acute cardiovascular or cerebrovascular events (such as acute cerebral infarction or myocardial infarction), significant trauma, acute pancreatitis, or other conditions that could precipitate stress-induced hyperglycemia. This also extends to those with concurrent endocrinopathies that may induce insulin resistance, such as Cushing's syndrome, hyperthyroidism, or pituitary growth hormone adenomas, as well as those currently receiving treatment with glucocorticoids or undergoing chemotherapy for malignancies.
• 2.Exclusion of individuals with a history of neurological disorders or psychiatric conditions that could impair cognitive function, as well as those with a history of medication use for these conditions.
• 3.Exclusion of individuals with severe complications of diabetes such as diabetic nephropathy in the uremic stage, or those with significant primary diseases of the cardiovascular, cerebrovascular, hepatic, renal, or hematopoietic systems, as well as individuals diagnosed with cancer.
• 4.Exclusion of individuals with communication barriers that could affect the assessment of cognitive function, including severe impairments in speech, vision, and hearing.
• 5.Individuals who have participated in other pharmacological clinical trials within the past month.
• 6.Individuals who have insufficient understanding of this study, are unwilling to participate, or, based on the researchers' judgment, present a reduced likelihood of enrollment or poor compliance due to unstable work and living locations or other factors that could lead to loss to follow-up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: experimental group; Take Buyuan Zhixiao Formula granules	Drug: Buyuan Zhixiao Formula; Buyuan Zhixiao Formula
Placebo Comparator: control group; Take a placebos	Drug: Placebo; The placebo contains 10% of the active ingredients of the Chinese medicine group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c	unit：%	Measured at 0, 3, 6, and 12 months respectively.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting blood glucose	unit：mmol/l	Measured at 0, 1, 2, 3, 4, 5, 6, 9, and 12 months respectively
2-hour postprandial blood glucose	unit：mmol/l	Measured at 0, 1, 2, 3, 4, 5, 6, 9, and 12 months respectively
blood pressure	unit：mmHg	Measured at 0, 1, 2, 3, 4, 5, 6, 9, and 12 months respectively
weight	unit：KG	Measured at 0, 1, 2, 3, 4, 5, 6, 9, and 12 months respectively
waist circumference	unit：cm	Measured at 0, 1, 2, 3, 4, 5, 6, 9, and 12 months respectively
BMI	unit：kg/m2	Measured at 0, 1, 2, 3, 4, 5, 6, 9, and 12 months respectively
Total Cholesterol	unit：mmol/l	Measured at 0, 3, 6, and 12 months
Triglycerides	unit：mmol/l	Measured at 0, 3, 6, and 12 months
High density lipoprotein cholesterol	unit：mmol/l	Measured at 0, 3, 6, and 12 months
Low density lipoprotein cholesterol	unit：mmol/l	Measured at 0, 3, 6, and 12 months
Ankle-Brachial Index（ABI）	The normal range for the ABI is generally considered to be from 0.9 to 1.3.	Measured at 0, 3, 6, and 12 months
Fasting insulin	unit：pmol/L	Measured at 0, 3, 6, and 12 months
C-peptide	unit：pmol/L	Measured at 0, 3, 6, and 12 months
insulin resistance index		Measured at 0, 3, 6, and 12 months
islet β-cell function index		Measured at 0, 3, 6, and 12 months
lipid Lipid accumulation product		Measured at 0, 3, 6, and 12 months
visceral adiposity index		Measured at 0, 3, 6, and 12 months
Measurement Results of Tumor Necrosis Factor-alpha Levels at Different Time Points		Measured at 0, 3, 6, and 12 months
Concentration Variation of Interleukin-10		Measured at 0, 3, 6, and 12 months
Change in Homocysteine Levels		Measured at 0, 3, 6, and 12 months
Average Concentration of Interleukin-6		Measured at 0, 3, 6, and 12 months
Change in Endothelin-1 Levels		Measured at 0, 3, 6, and 12 months
Average Concentration of Nitric Oxide		Measured at 0, 3, 6, and 12 months
Concentration Variation of Von Willebrand Factor		Measured at 0, 3, 6, and 12 months
Measurement Results of Vascular Endothelial Growth Factor Levels at Different Time Points		Measured at 0, 3, 6, and 12 months
Change in Matrix Metalloproteinase-9 Levels" or "Participants' Matrix Metalloproteinase-9 Concentration		Measured at 0, 3, 6, and 12 months
Average Concentration of Soluble Intercellular Adhesion Molecule-1		Measured at 0, 3, 6, and 12 months
Change in Serum Tau Protein Levels		Measured at 0, 3, 6, and 12 months
Average Concentration of Aβ40		Measured at 0, 3, 6, and 12 months
Average Concentration of Aβ42		Measured at 0, 3, 6, and 12 months
Change in Neurofilament Light Chain Protein Levels		Measured at 0, 3, 6, and 12 months
Carotid Ultrasound; Carotid Intima-Media Thickness.		Measured at 0, 6, and 12 months
Activities of Daily Living Scale score; Fried Frailty Phenotype Scale; Mini Nutritional Rating Scale; MoCA scale score; Traditional Chinese Medicine Kidney Deficiency and Blood Stasis Syndrome Scale score.		Measured at 0, 3, 6, and 12 months
Montreal Cognitive Assessment Score	The maximum score is 30 points, and the higher the score, the better the cognitive function.	Measured at 0, 3, 6, and 12 months
Fried Frailty Phenotype Scale	Those who have 5 or more of the items in the table can be diagnosed as frailty syndrome; those with less than 3 items are in the early stage of frailty; 0 items are healthy elderly people without frailty.	Measured at 0, 3, 6, and 12 months
Activities of Daily Living Scale score	The scale consists of 10 items, with a total score of 100 points. The Cronbach's alpha of the scale is 0.813. A score of 100 points is considered normal, while scores below 100 indicate a decline.A score of 100 points indicates full independence in daily living, without any dependency; 61-99 points suggest mild dependency; 41-60 points indicate moderate dependency; ≤40 points denote severe dependency.	Measured at 0, 3, 6, and 12 months
Mini Nutritional Rating Scale	The total score is 14 points, with the Cronbach's alpha of the scale being 0.906. A score of ≤7 points is considered malnourished, 8-11 points indicate a risk of malnutrition, and 12-14 points are indicative of normal nutrition. The total score is 14 points, with the Cronbach's alpha of the scale being 0.906. A score of ≤7 points is considered malnourished, 8-11 points indicate a risk of malnutrition, and 12-14 points are indicative of normal nutrition.	Measured at 0, 3, 6, and 12 months
Serum and urine metabolomics	Inferring the potential biological mechanisms of the effect of Buyuan Zhixiao Formula based on the differences in metabolic products in the blood and urine between the experimental and control groups.	Measured at 0 and 6 months respectively

Collaborators and Investigators

• Sponsor: Qing Ni
• Investigators: Principal Investigator: Qing Ni, postgraduate, China Academy of Chinese Medical Sciences Guang'anmen Hospital

Publications and helpful links

General Publications

• Nunes BP, Flores TR, Mielke GI, Thume E, Facchini LA. Multimorbidity and mortality in older adults: A systematic review and meta-analysis. Arch Gerontol Geriatr. 2016 Nov-Dec;67:130-8. doi: 10.1016/j.archger.2016.07.008. Epub 2016 Aug 2.
• Sinclair A, Saeedi P, Kaundal A, Karuranga S, Malanda B, Williams R. Diabetes and global ageing among 65-99-year-old adults: Findings from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2020 Apr;162:108078. doi: 10.1016/j.diabres.2020.108078. Epub 2020 Feb 14.
• Quinones AR, Markwardt S, Botoseneanu A. Diabetes-Multimorbidity Combinations and Disability Among Middle-aged and Older Adults. J Gen Intern Med. 2019 Jun;34(6):944-951. doi: 10.1007/s11606-019-04896-w. Epub 2019 Feb 27.
• Ji L, Hu D, Pan C, Weng J, Huo Y, Ma C, Mu Y, Hao C, Ji Q, Ran X, Su B, Zhuo H, Fox KA, Weber M, Zhang D; CCMR Advisory Board; CCMR-3B STUDY Investigators. Primacy of the 3B approach to control risk factors for cardiovascular disease in type 2 diabetes patients. Am J Med. 2013 Oct;126(10):925.e11-22. doi: 10.1016/j.amjmed.2013.02.035. Epub 2013 Jun 27.
• Carnethon MR, Biggs ML, Barzilay J, Kuller LH, Mozaffarian D, Mukamal K, Smith NL, Siscovick D. Diabetes and coronary heart disease as risk factors for mortality in older adults. Am J Med. 2010 Jun;123(6):556.e1-9. doi: 10.1016/j.amjmed.2009.11.023.
• Al Slail FY, Abid O, Assiri AM, Memish ZA, Ali MK. Cardiovascular risk profiles of adults with type-2 diabetes treated at urban hospitals in Riyadh, Saudi Arabia. J Epidemiol Glob Health. 2016 Mar;6(1):29-36. doi: 10.1016/j.jegh.2015.07.004. Epub 2015 Aug 6.
• Al-Maskari F, El-Sadig M, Nagelkerke N. Assessment of the direct medical costs of diabetes mellitus and its complications in the United Arab Emirates. BMC Public Health. 2010 Nov 8;10:679. doi: 10.1186/1471-2458-10-679.
• Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of Type 2 Diabetes - Global Burden of Disease and Forecasted Trends. J Epidemiol Glob Health. 2020 Mar;10(1):107-111. doi: 10.2991/jegh.k.191028.001.
• Ramtahal R, Khan C, Maharaj-Khan K, Nallamothu S, Hinds A, Dhanoo A, Yeh HC, Hill-Briggs F, Lazo M. Prevalence of self-reported sleep duration and sleep habits in type 2 diabetes patients in South Trinidad. J Epidemiol Glob Health. 2015 Dec;5(4 Suppl 1):S35-43. doi: 10.1016/j.jegh.2015.05.003. Epub 2015 Jun 11.

Study record dates

Study Major Dates

• Study Start (Estimated): May 6, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: April 2, 2024
• First Submitted That Met QC Criteria: April 6, 2024
• First Posted (Actual): April 10, 2024

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 6, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Endocrine System Diseases; Diabetes Mellitus; Metabolic Diseases
• Other Study ID Numbers: 2024-003-KY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No