Phase IV Trial to Evaluate Efficacy of Alpha-Lipoic Acid in Treating Symptomatic Diabetic Polyneuropathy in Egypt

NCT ID: NCT05813496

Last Updated: 2025-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 430 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-26
• Study Completion Date: 2024-12-11

Brief Summary

The purpose of the study is to find out whether ALA is effective and safe for treating Egyptian diabetic patients with symptomatic polyneuropathy. The ADA stated that despite the exploration of several pharmacological therapies for DPN management, substantial evidence on medicines that modify the natural history of DPN is still absent. This is a multicenter, interventional, two-arm, parallel-group, randomized, double-blinded, placebo-controlled, phase IV trial. Patients will be administered either one tablet of placebo or one tablet containing 600 mg of ALA twice a day for 24 weeks, depending on the randomization process.

Detailed Description

This is a multicenter, interventional, two-arm, parallel-group, randomized, double-blinded, placebo-controlled, phase IV trial to evaluate the efficacy and safety of ALA in the treatment of diabetic patients with symptomatic polyneuropathy in Egypt.

Patients will be randomly assigned to receive either :

• One tablet of 600 mg ALA twice a day orally for 24 weeks. Total daily dose during the study duration (24 weeks) = 1200 mg. , or
• One tablet of placebo twice a day orally for 24 weeks.
• The standard of Care (SOC) treatments will be prescribed for both study arms (Experimental and control arm) as per the routine clinical practice and following the relevant clinical guidelines. The SOC treatments include those for glycemic control and other treatments for the management of painful diabetic polyneuropathy; when needed through the course of the clinical study. As per the ADA and NICE guidelines (ADA, 2022) ("Type 2 Diabetes Adults Manag.," 2022); Pregabalin, Duloxetine, or Gabapentin are recommended as initial pharmacologic treatments for neuropathic pain in diabetes.

Estimated recruitment period: 24 weeks Estimated duration of participation: 24 weeks of treatment in addition to a screening period of approximately 1 week Visit 1: Screening/Baseline visit Visit 2: After 4 weeks ± 5 days of treatment Visit 3 (Phone call 1): After 12 weeks ± 15 days of treatment Visit 4 (Phone call 2): After 20 weeks ± 15 days of treatment Visit 5: After 24 weeks ± 15 days of treatment

Conditions

Polyneuropathy, Diabetic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

IND Arm

200 patients will receive one tablet of 600 mg of alpha-lipoic acid twice a day orally for 24 weeks.

Group Type: EXPERIMENTAL

Alpha-Lipoic Acid (ALA)

Intervention Type: DRUG

Oral tablet

Placebo Arm

200 patients will receive one tablet of placebo twice a day orally for 24 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Microcrystalline cellulose (Ph 101) 427.5 mg, Magnesium stearate 71.25 mg, Sodium laurayl sulphate 6 mg, Croscarmellose sodium 11.25 mg, Silica, colloid anhydrous 11.25 mg, and Purified talc 30 mg.

Interventions

Alpha-Lipoic Acid (ALA)

Oral tablet

Intervention Type: DRUG

Placebo

Microcrystalline cellulose (Ph 101) 427.5 mg, Magnesium stearate 71.25 mg, Sodium laurayl sulphate 6 mg, Croscarmellose sodium 11.25 mg, Silica, colloid anhydrous 11.25 mg, and Purified talc 30 mg.

Intervention Type: DRUG

Other Intervention Names

Thiotacid® 600 mg; Oral tablet

Eligibility Criteria

Inclusion Criteria

1. Signed informed consent form.

2. Male or female patients aged ≥ 18 and ≤ 64 years.

3. Type 2 diabetes mellitus (T2DM) patients as defined according to the American Diabetes Association (ADA) criteria with diabetes duration ≥ 1 year.

4. Hemoglobin A1c (HbA1c) ≤10%.

5. Patients with symptomatic distal symmetrical polyneuropathy (DSPN) attributable to diabetes; after a thorough evaluation for other causes of neuropathy, with evidence of polyneuropathy based on abnormal peripheral nerve function according to clinical and electrophysiological examinations.

6. Patients treated with oral antidiabetic drugs and/or insulin.

7. Patients with the treatment regimen, weight, diet, and physical activity level relatively acceptable as judged by the investigator within 1 month prior to study entry.

8. Patients with working telephone numbers.

Exclusion Criteria

1. Female patients with child-bearing potential not using effective birth control methods including oral contraceptives with a stable regimen for at least 2 months, depo-medroxyprogesterone, a barrier method alone (diaphragm, condoms, or contraceptive sponge with spermicidals), or an intrauterine device that has been in place for at least 2 months.

2. Patients with neuropathies other than DSPN; myopathy and other neurologic diseases that might interfere with the assessment of the severity of DSPN.

3. Patients with a recent history of drug or alcohol abuse; within 1 year prior to study entry.

4. Patients with a history of peripheral vascular disease and/or foot ulcers.

5. Patients with a history of organ transplantation.

6. Patients with a history of cardiovascular, pulmonary, gastrointestinal, hematologic, or endocrine disease, or malignancy that cause neuropathic pain.

7. Hospitalization due to hypoglycemia or ketoacidosis within 3 months prior to study entry.

8. Patients with significant hepatic or renal disease [Serum creatinine > 1.8 mg/dL for men and > 1.6 mg/dL for women, Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3 times upper limit of normal (ULN)].

9. Use of medications indicated for neuropathic pain relief within 15 days (washout period) prior to study entry. For analgesia, standard doses of salicylates, ibuprofen, indoles, fenamates, oxicams, or pyrazoles are allowed.

10. Use of antioxidants (including but not limited to vitamin E, vitamin C, and β-carotene) or pentoxifylline within 1 month prior to study entry.

11. Use of medications or vitamins known to cause peripheral neuropathy including but not limited to the use of phenytoin or carbamazepine over 15 or more years, or use of pyridoxine > 100 mg/d within 12 months prior to study entry.

12. Use of ≥ 50 mg ALA or use of alpha-linolenic acid-containing substances within 3 months prior to study entry.

13. Use of an investigational drug within 6 months prior to study entry.

14. Enrollment in any other clinical trial during the time of this trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MARC-CRO

UNKNOWN

Sponsor Role: collaborator

Eva Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Samir H Assaad Khali, PhD

Role: PRINCIPAL_INVESTIGATOR

Alexandria University Hospital / Internal Medicine

Mohamed R Halawa, PhD

Role: PRINCIPAL_INVESTIGATOR

Ain-Shams University Hospital / Internal Medicine

Nabil AF El Kafrawy, PhD

Role: PRINCIPAL_INVESTIGATOR

Menoufia University Hospital / Internal Medicine

Hanan M El Sotouhy Gawish, PhD

Role: PRINCIPAL_INVESTIGATOR

Mansoura University Hospital / Internal Medicine

Khaled ES El Hadidy, PhD

Role: PRINCIPAL_INVESTIGATOR

Beni Suef University Hospital / Internal Medicine

Locations

Alexandria University

Alexandria, Bab Sharqi, Egypt

Beni Suef University Hospital

Banī Suwayf, Beni Suweif Governorate, Egypt

Ain-Shams University Hospital

Cairo, Heliopolis, Egypt

Menoufia University Hospital

Shibīn al Kawm, Shebin El Kom, Egypt

Mansoura University Hospital

Al Mansurah, , Egypt

Countries

Egypt

References

ADA. (2022). Standards of Medical Care in Diabetes-2022 Th E Jou R Nal of C Li N Ical an D Appli Ed R Esearc H an D Education. Diabetes Care, 45(Suppliment 1), S1-S264. https://doi.org/10.2337/dc22-SREV

Reference Type: BACKGROUND

Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, Malik RA, Maser RE, Sosenko JM, Ziegler D; American Diabetes Association. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005 Apr;28(4):956-62. doi: 10.2337/diacare.28.4.956. No abstract available.

Reference Type: BACKGROUND

PMID: 15793206 (View on PubMed)

Pop-Busui R, Boulton AJ, Feldman EL, Bril V, Freeman R, Malik RA, Sosenko JM, Ziegler D. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care. 2017 Jan;40(1):136-154. doi: 10.2337/dc16-2042. No abstract available.

Reference Type: BACKGROUND

PMID: 27999003 (View on PubMed)

Roman-Pintos LM, Villegas-Rivera G, Rodriguez-Carrizalez AD, Miranda-Diaz AG, Cardona-Munoz EG. Diabetic Polyneuropathy in Type 2 Diabetes Mellitus: Inflammation, Oxidative Stress, and Mitochondrial Function. J Diabetes Res. 2016;2016:3425617. doi: 10.1155/2016/3425617. Epub 2016 Dec 12.

Reference Type: BACKGROUND

PMID: 28058263 (View on PubMed)

Type 2 diabetes in adults: management. (2022). Type 2 Diabetes in Adults: Management, March. https://www.ncbi.nlm.nih.gov/books/NBK553486/

Reference Type: BACKGROUND

Young MJ, Boulton AJ, MacLeod AF, Williams DR, Sonksen PH. A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia. 1993 Feb;36(2):150-4. doi: 10.1007/BF00400697.

Reference Type: BACKGROUND

PMID: 8458529 (View on PubMed)

Ziegler D, Gries FA. Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic neuropathy. Diabetes. 1997 Sep;46 Suppl 2:S62-6. doi: 10.2337/diab.46.2.s62.

Reference Type: BACKGROUND

PMID: 9285502 (View on PubMed)

Other Identifiers

Cl_Tr_17122019

Identifier Type: -

Identifier Source: org_study_id