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

March 21, 2025 updated by: Eva Pharma

A Multicenter, Interventional, Two-arm, Parallel-group, Randomized, Double-blinded, Placebo-controlled, Phase IV Trial to Evaluate the Efficacy of Alpha-Lipoic Acid in the Treatment of Symptomatic Diabetic Polyneuropathy in Egypt

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

430

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Mansoura, Egypt
        • Mansoura University Hospital
    • Bab Sharqi
      • Alexandria, Bab Sharqi, Egypt, 21544
        • Alexandria University
    • Beni-Suef
      • Banī Suwayf, Beni-Suef, Egypt, 2711860
        • Beni suef University hospital
    • Heliopolis
      • Cairo, Heliopolis, Egypt, 11588
        • Ain-Shams University Hospital
    • Shebin El Kom
      • Shibīn al-Kawm, Shebin El Kom, Egypt
        • Menoufia University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IND Arm
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)
Oral tablet
Other Names:
  • Thiotacid® 600 mg
Placebo Comparator: Placebo Arm
200 patients will receive one tablet of placebo twice a day orally for 24 weeks.
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.
Other Names:
  • Oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To compare the relative change in NCS parameters between the study arms
Time Frame: After four weeks of treatment
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
To compare the relative change in NCS parameters between the study arms.
Time Frame: After 24 weeks of treatment
The efficacy of alpha-lipoic acid in comparison with placebo in diabetic patients with symptomatic polyneuropathy assessed by the change in NCS after 24 weeks of treatment using student t-test (Mann-Whitney test for non-parametric data) to compare relative change between treatment arm and control arm.
After 24 weeks of treatment
To compare the relative change in NDS and Neuro-QoL between the study arms.
Time Frame: After 24 weeks of treatment
The efficacy of alpha-lipoic acid in comparison with placebo in diabetic patients with symptomatic polyneuropathy as assessed by the change in NDS* total score (out of 10 = the sum of the scores for right and left sides) using student t-test (Mann-Whitney test for non-parametric data) to compare relative change between treatment and control arms.
After 24 weeks of treatment
To compare the frequency of the need to rescue analgesic medications between the study arms
Time Frame: After 24 weeks of treatment
The efficacy alpha-lipoic acid in comparison with placebo in diabetic patients with symptomatic polyneuropathy assessed by number of patients receiving rescue analgesic medications using chi square test to compare 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 evaluable primary endpoint
After 24 weeks of treatment
To assess safety of Thiotacid® as per the nature and severity of the recorded adverse events.
Time Frame: After 24 weeks of treatment
The safety of alpha-lipoic acid in diabetic patients with symptomatic neuropathy assessed by the number of patients experiencing AE/SAE and number of patients who discontinued study drug due to AEs. These will be described using counts/percentages with 95% CI. This analysis will be descriptive and will be conducted on all patients enrolled to the study who signed an ICF.
After 24 weeks of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eva Pharma

Collaborators

MARC-CRO

Investigators

  • Principal Investigator: 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 26, 2022

Primary Completion (Actual)

August 3, 2024

Study Completion (Actual)

December 11, 2024

Study Registration Dates

First Submitted

April 3, 2023

First Submitted That Met QC Criteria

April 3, 2023

First Posted (Actual)

April 14, 2023

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 21, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Cl_Tr_17122019

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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