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

NCT05813496 | Completed Phase 4 DMC

• 1 other identifier: Cl_Tr_17122019
• Study Type: interventional
• Target: 430
• Locations: 1 country
• Sites: 5

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.

Conditions

Polyneuropathy, Diabetic

Keywords

Thiotacid; Double-blinded; Placebo-controlled; Multi-center

Outcome Measures

Primary Outcomes (1)

• To compare the relative change in NCS parameters between the study arms

  The main objective of this study is to calculate the efficacy of alpha-lipoic acid in comparison with placebo in diabetic patients with symptomatic polyneuropathy assessed by the change in NCS parameters after 4 weeks of treatment using student t-test (Mann-Whitney test for non-parametric data) to compare relative change between treatment arm and control arm. This analysis will be comparative and will be done on eligible subjects without protocol violation and who have at least one treatment dose and an evaluable primary endpoint.

  After four weeks of treatment

Secondary Outcomes (4)

• To compare the relative change in NCS parameters between the study arms.

  After 24 weeks of treatment

• To compare the relative change in NDS and Neuro-QoL between the study arms.

  After 24 weeks of treatment

• To compare the frequency of the need to rescue analgesic medications between the study arms

  After 24 weeks of treatment

• To assess safety of Thiotacid® as per the nature and severity of the recorded adverse events.

  After 24 weeks of treatment

Study Arms (2)

IND Arm

EXPERIMENTAL

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

Drug: Alpha-Lipoic Acid (ALA)

Placebo Arm

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Alpha-Lipoic Acid (ALA) DRUG

Oral tablet

Also known as: Thiotacid® 600 mg

IND Arm

Placebo 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.

Also known as: Oral tablet

Placebo Arm

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent form.
• Male or female patients aged ≥ 18 and ≤ 64 years.
• Type 2 diabetes mellitus (T2DM) patients as defined according to the American Diabetes Association (ADA) criteria with diabetes duration ≥ 1 year.
• Hemoglobin A1c (HbA1c) ≤10%.
• 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.
• Patients treated with oral antidiabetic drugs and/or insulin.
• 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.
• Patients with working telephone numbers.

You may not qualify if:

• 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.
• Patients with neuropathies other than DSPN; myopathy and other neurologic diseases that might interfere with the assessment of the severity of DSPN.
• Patients with a recent history of drug or alcohol abuse; within 1 year prior to study entry.
• Patients with a history of peripheral vascular disease and/or foot ulcers.
• Patients with a history of organ transplantation.
• Patients with a history of cardiovascular, pulmonary, gastrointestinal, hematologic, or endocrine disease, or malignancy that cause neuropathic pain.
• Hospitalization due to hypoglycemia or ketoacidosis within 3 months prior to study entry.
• Patients with significant hepatic or renal disease \[Serum creatinine \> 1.8 mg/dL for men and \> 1.6 mg/dL for women, Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3 times upper limit of normal (ULN)\].
• 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.
• Use of antioxidants (including but not limited to vitamin E, vitamin C, and β-carotene) or pentoxifylline within 1 month prior to study entry.
• 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.
• Use of ≥ 50 mg ALA or use of alpha-linolenic acid-containing substances within 3 months prior to study entry.
• Use of an investigational drug within 6 months prior to study entry.
• Enrollment in any other clinical trial during the time of this trial.

Sponsors & Collaborators

• Eva Pharma: lead
• MARC-CRO: collaborator

Study Sites (5)

Alexandria University

Alexandria, Bab Sharqi, 21544, Egypt

Location

Beni Suef University Hospital

Banī Suwayf, Beni Suweif Governorate, 2711860, Egypt

Location

Ain-Shams University Hospital

Cairo, Heliopolis, 11588, Egypt

Location

Menoufia University Hospital

Shibīn al Kawm, Shebin El Kom, Egypt

Location

Mansoura University Hospital

Al Mansurah, Egypt

Location

Related Publications (7)

• 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

  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.

  PMID: 15793206 BACKGROUND

• 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.

  PMID: 27999003 BACKGROUND

• 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.

  PMID: 28058263 BACKGROUND

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

  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.

  PMID: 8458529 BACKGROUND

• 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.

  PMID: 9285502 BACKGROUND

MeSH Terms

Conditions

Diabetic Neuropathies

Interventions

Thioctic Acid; Tablets

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Carboxylic Acids; Organic Chemicals; Thiophenes; Sulfur Compounds; Coenzymes; Enzymes and Coenzymes; Fatty Acids; Lipids; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Samir H Assaad Khali, PhD

  Alexandria University Hospital / Internal Medicine

  PRINCIPAL INVESTIGATOR

• Mohamed R Halawa, PhD

  Ain-Shams University Hospital / Internal Medicine

  PRINCIPAL INVESTIGATOR

• Nabil AF El Kafrawy, PhD

  Menoufia University Hospital / Internal Medicine

  PRINCIPAL INVESTIGATOR

• Hanan M El Sotouhy Gawish, PhD

  Mansoura University Hospital / Internal Medicine

  PRINCIPAL INVESTIGATOR

• Khaled ES El Hadidy, PhD

  Beni Suef University Hospital / Internal Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: After signing the ICF, eligible patients were randomized in a 1:1 allocation ratio, into one of the two treatment groups, to receive either ALA or placebo. Randomization will be done using an interactive web response system (IWRS). Randomization was stratified by baseline body mass index (BMI) (\< 25 Kg/m2 or 25-40 Kg/m2) followed by age (\<45 years or ≥ 45 years) and gender (male or female).

Study Record Dates

• First Submitted: April 3, 2023
• First Posted: April 14, 2023
• Study Start: October 26, 2022
• Primary Completion: August 3, 2024
• Study Completion: December 11, 2024
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

EG (5)