Alpha Lipoic Acid for Treatment of Diabetic Neuropathy

February 2, 2016 updated by: Hector Garcia-Alcala, Universidad Popular Autónoma del Estado de Puebla

Treatment With Alpha-lipoic Acid Over 16 Weeks in Type 2 Diabetic Patients With Symptomatic Polyneuropathy Who Responded to Initial 4-week High-dose Loading

Patients with diabetic neuropathy and total symptoms score(TSS) >7 points were invited to this open multicenter study. Patients were free of pain medications and severe diabetic complications .Patients started alpha lipoic acid (ALA)1800 mg for 4 weeks. Patients with a decrease >3 points in the TSS were randomly allocated to 600 mg of ALA (ALA group) or no medications (ALA withdrawal) for 16 weeks. In each visit investigators evaluated any change in the TSS and the necessity of rescue medication to control symptoms (mainly pain). At the end of the study investigators compared between ALA and ALA withdrawal groups TSS levels and the frequency of use of rescue medications. Physicians were free to manage glucose to maintain Hba1c close to the ADA target (HbA1c <7%).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This trial was conducted in accordance with the Declaration of Helsinki and was approved by the ethics committee of Universidad Popular Autónoma del Estado de Puebla, Mexico. All participants provided a written informed consent. Type 2 diabetic patients (according to American Diabetes Association (ADA) criteria) with symptomatic diabetic sensorimotor polyneuropathy (DSPN) defined as the presence of neuropathic symptoms (pain, paresthesias, or numbness) were invited to participate in this open-label multicenter trial. Inclusion criteria were: total symptom score (TSS) >7 points, HbA1c<10%, and serum creatinine <2 mg/dl. Exclusion criteria were evidence of active cardiovascular disease, malignancy, or any other conditions causing neuropathic pain, use of analgesic, antidepressant, or antiepileptic drugs, or any other medication aimed to relief neuropathic pain. In addition, child-bearing female patients not using any effective birth control method and under surveillance of a board-certified gynecologist were excluded.

Phase 1. All patients meeting inclusion criteria received 600 mg of alpha lipoic acid (ALA) (Meda Pharma, Germany) orally tid, 30 min after each main meal for 4 weeks. During phase 1, no medication for relief of neuropathic pain was allowed. Each participating site was in charge to maintain glycemic control based on the investigator's judgment attempting that all patients were treated according to the american diabetes association (ADA) guidelines. All patients were seen once a week, and at each site visit, TSS was assessed along with a pill count to ensure drug adherence, presence of adverse events and, if needed, treatment adjustments to maintain glucose levels within the ADA targets. Patients with a TSS reduction >3 points by the end of phase 1 were selected to proceed with phase 2 of the study. Patients with a decrease <3 points in TSS or that used other neuropathic pain drugs were excluded from study phase 2.

Phase 2. Patients with a decrease of ≥3 TSS points after phase 1 were randomized to receive 600 mg of ALA orally qd for 16 weeks or ALA withdrawal. Patients were scheduled to visit the clinic every 2-3 weeks for TSS, monofilament and assessment. If needed, the patient was prescribed analgesic rescue medication which was monitored at each visit. Primary endpoint was the change in TSS in the two groups studied in phase 2 and the frequency of use of rescue medications Neurological examination was performed at baseline and after phase 1 and 2 including the monofilament test, vibration perception threshold (VPT), and ankle reflexes. A 10g nylon monofilament (Thio-Feel ® Meda Pharma, Germany) was applied to four anatomical sites in each foot (1st, 3rd and 5th metatarsal heads and plantar surface of distal hallux) as previously described (correct answer = 1 point, with a maximum of 4 points in each foot). Eight correct answers were considered normal, 1-7 correct answers indicated reduced monofilament sensation, while absent sensation was assumed if no answer was correct. VPT was evaluated using a 128-Hz tuning fork (Thio-Vib ®, Meda Pharma,Germany) applied bilaterally at the tip of the great toe. Responses were categorized as abnormal (no perception of vibration), present (examiner perceives vibration <10 seconds after patient reported disappearance of vibration perception) and reduced (examiner perceives vibration >10 sec after patient reported disappearance of vibration perception). Ankle reflexes were graded as normal, decreased, and absent

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 4

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Type 2 diabetic patients (according to American Diabetes Association (ADA) criteria)
  • Symptomatic diabetic polyneuropathy
  • Total Symptom Score (TSS) >7 points,
  • HbA1c<10%,
  • Serum creatinine <2 mg/dl.

Exclusion Criteria:

  • Active cardiovascular disease
  • Malignancy
  • Any other conditions causing neuropathic pain
  • Use of analgesic, antidepressant, or antiepileptic drugs, or any other medication aimed to relief neuropathic pain.
  • Child-bearing female patients not using any effective birth control method and under surveillance of a board-certified gynecologist

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: alpha lipoic acid treatment
After a decrease in the total symptoms score >3 points with 600 mg orally tid of alpha lipoic acid for 4 weeks patients were randomized to recieve for 16 weeks 600 mg orally once a day of alpha lipoic acid
Drug: Alpha lipoic acid
Alpha lipoic acid 1800 mg PO divided in 3 doses for 4 weeks . If total symptoms score decreased >3 points patients received alpha lipoic acid 600 mg PO each day or no treatment for 16 weeks.
Other Names:
  • Thioctic acid
  • Thioctacid HR
No Intervention: alpha lipoic acid withdrawal
After a decrease in the total symptoms Score >3 points with 600 mg orally tid of alpha lipoic acid for 4 weeks patients were randomized to recieve for 16 weeks no treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Symptoms Score
Time Frame: 20 weeks
Total symptoms score is a summation of presence, severity, and duration of the four main positive neuropathic sensory symptoms: lancinating/stabbing pain, burning pain, paresthesia, and asleep numbness
20 weeks

Collaborators and Investigators

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

Sponsor

Universidad Popular Autónoma del Estado de Puebla

Investigators

  • Principal Investigator: Hector Garcia-Alcala, MD, Universidad Popular Autónoma del Estado de Puebla

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

December 1, 2009

Primary Completion (Actual)

December 1, 2010

Study Completion (Actual)

December 1, 2010

Study Registration Dates

First Submitted

May 4, 2015

First Submitted That Met QC Criteria

May 6, 2015

First Posted (Estimate)

May 12, 2015

Study Record Updates

Last Update Posted (Estimate)

March 2, 2016

Last Update Submitted That Met QC Criteria

February 2, 2016

Last Verified

February 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UPAEP25082009

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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