Role of Synchronized Lifestyle Modification Program on Diabetic Neuropathy Taking Oral Hypoglycemics

Diabetic Neuropathies Clinical Trial

Official title:

Role of Synchronized Lifestyle Modification Program on Diabetic Peripheral Neuropathy Patients Taking Oral Hypoglycemics and GLP-1 Analogues

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04813146
• Other study ID #: IRC/20/234 Rubab Rameez
• Status: Recruiting
• Phase: N/A
• Start date: February 5, 2021
• Est. completion date: January 30, 2022

Study information

• Verified date: March 2021
• Source: Riphah International University
• Contact: Imran Amjad, PhD
• Phone: 03324390125
• Email: imran.amjad[@]riphah.edu.pk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to determine the combined effect of SLP along with Physiotherapy in improving Type 2 DPN patients taking OHAs and GLP-1 analogues.

Description:

Diabetes mellitus (DM) is a chronic metabolic disease defined by persistently increased blood glucose levels with fasting blood glucose ≥ 126 mg/dl, random plasma glucose ≥ 200mg/dl and HbA1c ≥ 6.5%.

Diabetes has emerged as a great socioeconomic burden for the developing world. In 2017, globally, 451 million people were affected with diabetes. In Pakistan, the prevalence of type 2 diabetes is 16.98% which differs significantly with age, education, body mass index (BMI), obesity, family history and blood pressure. DM is classified into type 1 diabetes (T1D) and type 2 diabetes (T2D). T1D occurs due to an autoimmune pancreatic beta cell destruction with consequent insulin deficiency whereas T2D occurs due to predominantly insulin resistance with relative insulin deficiency or defective secretion. T2D cause serious and chronic microvascular and macrovascular complications. One of the most prevalent microvascular complication is diabetic peripheral neuropathy (DPN). DPN is defined as distal, symmetric sensorimotor polyneuropathy as a result of hyperglycemia and microangiopathy. It is a demyelinating disease of peripheral nerve fibers that manifests as parasthesias, impairment of sensations of vibration, proprioception, touch, pressure, pain and temperature.

Risk factors of DPN are age, duration of diabetes, HbA1c >7.0%, increased BMI, hyperlipidemia and hyperglycemia. Treatment of T2D is targeted towards good glycemic control that includes life style modifications i.e. diet and exercise, oral hypoglycemic agents (OHAs) and subcutaneous insulin administration. In life style modification, variety of exercises are recommended that help to slow the progression of peripheral neuropathy.These include; aerobic training, weight-bearing, static and dynamic balance training and strength training exercises which improve the gait speed, stride length and nerve conduction velocities (NCVs) of sensory and motor nerves while flexibility exercises improve the range-of-motion in ankle, hip and shoulder joints and keep them flexible. Importance of dietary modification is enhanced if it is synchronized with the circadian rhythm of the body. Therefore, Synchronized Lifestyle Modification Program (SLP) is a personalized, homeostasis restoring, liver centric lifestyle modification program that works through the correction of body clock rhythm. Lifestyle medicine is defined as the discipline of studying how daily habits and practices impact both on the prevention and treatment of disease. Its key aspects are: regular physical activity, proper nutrition, weight management, avoiding tobacco and a sound mental health. Lifestyle modification in diabetics is believed to enhance the function of pancreatic islet cells and induce glucose-stimulated insulin release.Regarding pharmacological treatment, following OHAs are used which are; biguanides, insulin secretagogues, alpha-glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP4) inhibitors and sodium glucose co-transporter-2 inhibitors. Now a days, an injectable agent i.e. Glucagon like peptide-1(GLP-1) receptor agonist is used with OHAs and is effective in decreasing blood glucose levels with a low risk of hypoglycemia in elderly patients.

Limited data is available which supports the combined effect of Synchronized Lifestyle modification Program (SLP) and Physiotherapy in the progression of DPN in T2D patients taking OHAs and GLP-1.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 216
• Est. completion date: January 30, 2022
• Est. primary completion date: January 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Gender includes both male and female

2. Patients between age group 40-75 years

3. Clinically diagnosed patients of Type 2 diabetes on OHAs and GLP-1 analogues

4. Diabetic patients with symptomatic peripheral neuropathy (Severity of DPN is associated with a physical examination score > 2.5 by using Michigan Neuropathy Screening Instrument (MNSI) with grades mild, moderate and severe)

Exclusion Criteria:

1. Type 1 diabetic patients

2. Age < 40 years and > 75 years

3. Patients with any other co-morbidities (Heart, liver and kidney diseases)

4. Patients with neuropathies due to any other disease

5. Orthopaedic and surgical procedure of lower limbs

6. Patients with foot ulcers

7. Peripheral vascular diseases

8. Patients receiving any structured supervised physiotherapy

9. Pregnant females

Related Conditions & MeSH terms

• Diabetic Neuropathies
• Peripheral Nervous System Diseases

Intervention

Other:
• SLP
Synchronization of dietary intake with circadian rhythm of the body
• SLP along with Physiotherapy
Synchronization of dietary intake along with Physiotherapy (aerobic, flexibility, resistance and balance exercises)
• Physiotherapy
Physiotherapy given only (aerobic, flexibility, resistance and balance exercises)

Locations

Country	Name	City	State
Pakistan	Pakistan Railway Hospital	Islamabad	Federal

Sponsors (1)

Lead Sponsor	Collaborator
Riphah International University

Country where clinical trial is conducted

Pakistan, 

References & Publications (13)

Aamir AH, Ul-Haq Z, Mahar SA, Qureshi FM, Ahmad I, Jawa A, Sheikh A, Raza A, Fazid S, Jadoon Z, Ishtiaq O, Safdar N, Afridi H, Heald AH. Diabetes Prevalence Survey of Pakistan (DPS-PAK): prevalence of type 2 diabetes mellitus and prediabetes using HbA1c: a population-based survey from Pakistan. BMJ Open. 2019 Feb 21;9(2):e025300. doi: 10.1136/bmjopen-2018-025300. — View Citation

Bae SA, Fang MZ, Rustgi V, Zarbl H, Androulakis IP. At the Interface of Lifestyle, Behavior, and Circadian Rhythms: Metabolic Implications. Front Nutr. 2019 Aug 28;6:132. doi: 10.3389/fnut.2019.00132. eCollection 2019. Review. — View Citation

Cancelliere P. A Review of the Pathophysiology and Clinical Sequelae of Diabetic Polyneuropathy in the Feet. J Diabetes, Metab Disord Control. 2016;3(2):21-4.

Gholami F, Nikookheslat S, Salekzamani Y, Boule N, Jafari A. Effect of aerobic training on nerve conduction in men with type 2 diabetes and peripheral neuropathy: A randomized controlled trial. Neurophysiol Clin. 2018 Sep;48(4):195-202. doi: 10.1016/j.neucli.2018.03.001. Epub 2018 Mar 30. — View Citation

Iqbal Z, Azmi S, Yadav R, Ferdousi M, Kumar M, Cuthbertson DJ, Lim J, Malik RA, Alam U. Diabetic Peripheral Neuropathy: Epidemiology, Diagnosis, and Pharmacotherapy. Clin Ther. 2018 Jun;40(6):828-849. doi: 10.1016/j.clinthera.2018.04.001. Epub 2018 Apr 30. Review. — View Citation

Khawandanah J. Double or hybrid diabetes: A systematic review on disease prevalence, characteristics and risk factors. Nutr Diabetes. 2019 Nov 4;9(1):33. doi: 10.1038/s41387-019-0101-1. — View Citation

Liu X, Xu Y, An M, Zeng Q. The risk factors for diabetic peripheral neuropathy: A meta-analysis. PLoS One. 2019 Feb 20;14(2):e0212574. doi: 10.1371/journal.pone.0212574. eCollection 2019. — View Citation

Majeedkutty NA, Jabbar MA, Sreenivasulu S. Physical therapy for diabetic peripheral neuropathy: A narrative review. Disabil CBR Incl Dev. 2019;30(1):112-25.

Marín-Peñalver JJ, Martín-Timón I, Sevillano-Collantes C, Del Cañizo-Gómez FJ. Update on the treatment of type 2 diabetes mellitus. World J Diabetes. 2016 Sep 15;7(17):354-95. doi: 10.4239/wjd.v7.i17.354. Review. — View Citation

Parr EB, Heilbronn LK, Hawley JA. A Time to Eat and a Time to Exercise. Exerc Sport Sci Rev. 2020 Jan;48(1):4-10. doi: 10.1249/JES.0000000000000207. — View Citation

Punthakee Z, Goldenberg R, Katz P. Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome. Can J Diabetes [Internet]. 2018;42:S10-5. Available from: https://doi.org/10.1016/j.jcjd.2017.10.003

Qaseem A, Barry MJ, Humphrey LL, Forciea MA; Clinical Guidelines Committee of the American College of Physicians. Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline Update From the American College of Physicians. Ann Intern Med. 2017 Feb 21;166(4):279-290. doi: 10.7326/M16-1860. Epub 2017 Jan 3. — View Citation

Rippe JM. Lifestyle Medicine: The Health Promoting Power of Daily Habits and Practices. Am J Lifestyle Med. 2018 Jul 20;12(6):499-512. doi: 10.1177/1559827618785554. eCollection 2018 Nov-Dec. Review. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Life style pattern assessment	Changes from baseline, assessed through a self-structured questionnaire consisting of open-ended questions to assess the timing and type of food taken in meals, daily water intake and sleeping habits. Total 10 questions are included.	12 weeks
Primary	Calculation of Body Mass Index	Changes from baseline calculated by measuring height in meters through a metal measuring tape and weight in kilograms through portable manual weighing scale. BMI with minimum value of 18.5 kilogram/ meters square (kg/m2) and maximum value of 24.9 kilogram /meters square (kg/m2). Below 18.5 kilograms/meters square (kg/m2) is considered as underweight and above 24.9 kilogram/meters square (kg/m2) is considered as obese.	12 weeks
Primary	Measurement of Systolic Blood pressure	Changes from baseline are assessed by using Mercury Sphygmomanometer with minimum value of 110 millimeter of mercury (mmHg) and the maximum value of 130 millimeter of mercury (mmHg). Below 110 millimeter of mercury (mmHg) is considered as low systolic blood pressure and above 130 millimeter of mercury (mmHg) is considered as high systolic blood pressure.	12 weeks
Primary	Measurement of Diastolic Blood pressure	Changes from baseline are assessed by using Mercury Sphygmomanometer with minimum value of 60 millimeter of mercury (mmHg) and the maximum value of 90 millimeter of mercury (mmHg). Below 60 millimeter of mercury (mmHg) is considered as low diastolic blood pressure and a value above 90 millimeter of mercury (mmHg) is considered as high diastolic blood pressure.	12 weeks
Primary	Michigan Neuropathy Screening Instrument	Changes from baseline is assessed. Subjective assessment is done by a questionnaire that is self-administered by the participants. Responses of "yes" are given to questions 1-3, 5-6, 8-9, 11-12, 14-15 and each of them counted as one point. A "no" response is given on questions 7 and 13 and are counted as 1 point. A score of more than or equal to 7 in the history questionnaire is considered abnormal. Lower extremity examination includes inspection and assessment of vibratory sensation and ankle reflexes which is considered as abnormal at a score of more than or equal to 2.5.	12 weeks
Primary	Peak latency of Sensory Nerves (Sural and Peroneal)	Changes from baseline is assessed through nerve conduction studies. Value of 4.2 millisecond (ms) of sural nerve and 6.1 millisecond (ms) for peroneal nerve is considered normal. Values below 4.2 millisecond (ms) and 6.1 millisecond (ms) are considered abnormal.	12 weeks
Primary	Amplitude of Sensory Nerves (Sural and Peroneal)	Changes from baseline are assessed through nerve conduction studies with a value of 6 microvolt (µV) for sural nerve and 2 microvolt (µV) for peroneal are considered normal. Values below 6 microvolt (µV) and 2 microvolt (µV) are considered abnormal.	12 weeks
Primary	Velocity of Sensory Nerves	Changes from baseline are assessed through nerve conduction studies with value of 41 meters/second (m/sec) is considered normal. Value below 41meters/second (m/sec) is considered abnormal.	12 weeks
Primary	Onset Latency of Motor Nerves (Peroneal and Tibial)	Changes from baseline are assessed through nerve conduction studies with value of 6.1 millisecond (ms) for both are considered normal. Value below 6.1 millisecond (ms) is considered abnormal.	12 weeks
Primary	Amplitude of Motor Nerves (Peroneal and Tibial)	Changes from baseline are assessed through nerve conduction studies with values of 2 millivolt (mV) and 3 millivolt (mV) are considered normal. Values below 2 millivolt (mV) and 3 millivolt (mV) are considered abnormal.	12 weeks
Primary	Velocity of Motor Nerves (Peroneal and Tibial)	Changes from baseline are assessed through nerve conduction studies with values of 41 meters/second (m/sec) is considered normal for both nerves. Value less than 41 meters/second (m/sec) is considered abnormal.	12 weeks
Primary	Assessment of Balance by Berg Balance Scale	Changes from baseline are assessed with Low Fall Risk 41-56, Medium Fall Risk 21-40, High Fall Risk 0-20.	12 weeks
Primary	Serum Fasting Blood Glucose	Changes from baseline are measured by Glucose oxidase enzyme based method in milligram/deciliter (mg/dL) using Glucometer with minimum value of 72 milligram/deciliter (mg/dL) and maximum value of 99 milligram/deciliter (mg/dL). Value below 72 milligram/deciliter (mg/dL) is considered hypoglycemic and above 99 milligram/deciliter (mg/dL) is hyperglycemic.	12 weeks
Primary	Serum Total Cholesterol	Changes from baseline are measured by Cholesterol oxidase enzyme based method with minimum value of 125 milligram/deciliter (mg/dL) and maximum value of 200 milligram/deciliter (mg/dL).	12 weeks
Primary	Serum Triglycerides	Changes from baseline are measured by Glycerol phosphate enzyme based method with minimum value of less than150 milligram/deciliter (mg/dL) and maximum value of199 milligram/deciliter (mg/dL).	12 weeks
Primary	Serum High Density Lipoproteins (HDL)	Changes from baseline are measured by Direct enzymatic immune-inhibition with minimum value of 40 milligram/deciliter (mg/dL) and maximum value of greater than 40 milligram/deciliter (mg/dL).	12 weeks
Primary	Serum Low Density Lipoproteins	Changes from baseline are measured by Friedewald calculation with minimum value of 100 milligram/deciliter (mg/dL) and maximum value of 129 milligram/deciliter (mg/dL).	12 weeks
Primary	Serum HbA1c concentration	Changes from baseline are measured by Ion exchange chromatography with minimum value of 4 % and maximum value of 5.9 %. Normal range for the HbA1c level is between 4% and 5.6%. Levels between 5.7% and 6.4% is the pre-diabetic range. Levels of 6.5% or higher is diabetic range.	12 weeks