Condition category
Nervous System Diseases
Date applied
12/12/2007
Date assigned
14/03/2008
Last edited
16/07/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Diabetes is often complicated by the development of diabetic nerve disease (neuropathy). Diabetic neuropathy affects nerves that are outside of the brain and spinal cord, such as nerves in the arms, legs, hands and feet. Symptoms of diabetic neuropathy may include pain, such as a feeling of burning, prickling, tingling, aching, pins and needles usually occurring on both sides of the body affecting hands, legs or feet. Some patients may not be able to distinguish between sharp and dull and hot and cold (altered sensation).
The aim of the study is to find out whether neuropathic pain in painful diabetic neuropathy is relieved by taking a tablet called taurine. Taurine occurs naturally in the body and it is thought that patients with painful diabetic neuropathy have less taurine in their body. By increasing the level of taurine in the body it is hoped that patients will experience less pain. This in turn may have the added benefit of improving quality of life.

Who can participate?
180 patients from Diabetic Clinics at Heartlands and Solihull (UK) will be invited to take part in this study. You are eligible to take part if you have developed the complication of diabetes known as neuropathy and are 18-70 years old.

What does the study involve?
The patients will be randomly split into two groups. One group will receive the experimental drug and the second group will receive a dummy (placebo). Patients will be asked to attend a study visit to determine whether they are suitable to take part in this study. Tests will include a physical assessment (such as blood pressure and weight). An electrocardiogram (a painless test that records the electrical activity of your heart) will be performed. You will also have tests to determine the extent of your neuropathy, including your response to vibratory stimulation (tuning fork), cold detection (the difference between hot and cold) and comparisons made between areas on your body where you have pain and where you don’t. You will have an Autonomic Nerve Function Test performed on you. The test is painless and helps the study doctor decide whether you have neuropathy. You will be requested to attend the clinic for monthly physical assessments, collection of pain diaries and collection of the study drug to measure compliance. At three months a physical assessment will be performed including the above mentioned assessments of neuropathy. At a second visit, the pain and sleep diaries will be collected and any adverse events recorded. The questionnaires will again be administered and the experimental drug collected to measure compliance to the study. Four weeks after the study is completed, you will be contacted to assess how you are feeling now that the study drug has been stopped.

What are the possible benefits and risks of participating?
We hope that the treatment will help the pain in your feet. However, this cannot be guaranteed. The information we get from this study may help us to treat future patients with painful diabetic neuropathy more effectively.

Where is the study run from?
The majority of the visits will be held at Heart of England NHS Foundation Trust, and at least two visits will be completed at the Queen Elizabeth Hospital, Birmingham (UK).

When is the study starting and how long is it expected to run for?
Patient recruitment started in October 2006. The study lasts for 12 weeks plus a follow-up visit a month after finishing the study drug.

Who is funding the study?
This study is funded by the National Institutes of Health (USA). It is organised and sponsored by the University of Birmingham (UK).

Who is the main contact?
Prof. Martin J. Stevens, m.j.stevens@bham.ac.uk
Clinical trial coordinator and research secretary: Kiran Dubb: +44 121 414 3718 and Sarah Ward: +44 121 424 0182

Trial website

Contact information

Type

Scientific

Primary contact

Prof Martin J. Stevens

ORCID ID

Contact details

University of Birmingham
The Medical School
Institute for Biomedical Research
Edgbaston
Birmingham
B45 8PF
United Kingdom
+44 (0)121 414 8162
m.j.stevens@bham.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

RG 05-126

Study information

Scientific title

Acronym

Study hypothesis

Our overall hypothesis is that taurine depletion contributes to the development of painful Diabetic Neuropathy (DN). The rationale is based on:
a. Evidence implicating oxidative stress, altered neuronal calcium signaling and neuronal hyperexcitability in the development of painful DN
b. The emerging role of taurine as an important endogenous antioxidant, calcium regulator, neurotrophin, modulator of neuronal hyperexcitability and analgesic
c. Our data implicating a critical role for taurine depletion and oxidative stress in the pathogenesis of experimental DN.
The experimental approach will be to utilize biochemical and electrophysiological techniques to evaluate the potential of taurine treatment alone to decrease pain in patients with DN. These studies will test a novel mechanistically-based therapeutic approach to a common disabling and often refractory complication of diabetes.

On 08/07/2013 the anticipated end date was modified, the initial anticipated end date was 30/06/2009

Ethics approval

Leeds (East) Research Ethics Committee, approved on 22/09/2006.

Study design

A randomised, blinded, parallel two-group clinical study.

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Diabetic neuropathy

Intervention

Taurine 3,000 mg/day (3 capsules) orally vs placebo 3 capsules daily for 12 weeks

Intervention type

Drug

Phase

Not Specified

Drug names

Taurine

Primary outcome measures

1. Short-Form McGill-Melzack Pain Questionnaire (SF-MMPQ) at baseline, 4, 8 and 12 weeks: A SF-MMPQ is used to determine the effects of taurine treatment on qualitative aspects of pain perception. The SF-MMPQ comprises a sensory score, an affective score and a total score for various pain descriptors; a Visual Analogue Scale (VAS) to assess overall pain intensity and a Present Pain rating Intensity index (PPI). The SF-MMPQ contains 15 descriptions of pain, 11 of which represent the sensory dimension of painful experience and 4 of which represent the affective dimension. Each of these pain descriptions is then ranked by the subject on a 4 point scale and totally within subclasses. The overall intensity of the pain is scored using the 6-point PPI and the VAS.
2. Daily pain diaries, recorded for 12 weeks.
3. Physician and Patient Global Assessment of Change, assessed at 12 weeks post inclusion into the study (final assessment)

Secondary outcome measures

1. Mean Sleep Interference Score: Decreased nocturnal pain perception may be associated with improved sleep. This will be assessed using a standardized sleep interference score. Mean sleep interference scores are calculated at baseline (i.e. the week preceding the randomization visit) and for the final week of the study (between visits B [physical exam] and C [neurological exam]). The diary that is utilized for sleep assessment comprises a daily diary with an 11-point Likert-type scale which describes the degree to which the subject's pain has interfered with sleep during the preceding 24 h. The scale ranges from zero (pain does not interfere with sleep) to 10 (pain completely interferes with sleep). The assessment is performed on a daily basis upon awakening. The end-point mean sleep interference score is calculated as the mean score for the last 7 dairy entries while the subject was taking the study drug.
2. Mean Pain Scores from Screening to Study End: The subjects daily diaries are used to compute the mean pain scores in each treatment group from the screening visit to the study end. The daily diary comprises an 11-point Likert-type scale which ranges from 0 (no pain) to 10 (worst possible pain). The degree of neuropathic pain that has been experienced by the subject is rated by selecting a number from 0 to 10. This diary is completed upon awakening. The end-point mean pain score is calculated as the mean score for the last 7 dairy entries while the subject was taking the study drug.
3. Clinical and Patient Global Impression of Change: These measures of global impression of change are evaluated by both the physician and the patient at the final visit (physical exam). The Clinical Global Impression of Change is a clinician-rated instrument which measures the change in the subjects overall status on a 7-point scale which ranges from 1 (very much improved) to 7 (very much worse). In parallel, the subject completes a Patient Global Impression of Change which measures the subjects overall status using a similar 7-point scale.

Overall trial start date

01/10/2006

Overall trial end date

01/12/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. Type 1 or type 2 diabetes as defined by the World Health Organization Classification
2. Duration of diabetes of at least 5 years
3. The HbA1c should be <10.5% with <1% fluctuation of HbA1c levels over the past 6 months
4. Age between 18 and 80 years
5. Women of childbearing potential must be using an acceptable method of contraception to prevent pregnancy when they are enrolled in the study and must agree to continue to practice an acceptable method of contraception for the duration of their participation in the study
6. Must meet the specified criteria for painful DN and have no risk factors for other causes for neuropathy
7. Willingness to sign the Center for Research Ethics Committee (COREC) approved informed consent form

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

180

Participant exclusion criteria

1. Nursing mothers, pregnant women (excluded by a negative pregnancy test)
2. Patients with a history of drug or alcohol dependence in the last 5 years
3. Patients with pre-existing cardiovascular disease
4. Patients with hypoxemic disease
5. Patients with severe systemic disease other than diabetes which has as a recognized complication neuropathy or severe chronic pain
6. Patients with symptoms of neuropathic pain in the upper limbs alone
7. Significant changes in skin conditions in the areas to be tested which could alter sensation
8. Subjects with a previous history of neuropathic foot ulceration or Charcot arthropathy
10. Patients currently taking medications that could affect symptoms of painful DN except paracetamol (up to 4 g/d) or aspirin (up to 325 mg/d)
11. Patients experiencing an increase in pain after analgesic medication washout to levels which would, in the view of the PI, require prohibited analgesic therapy within a 12 week period
12. Patients whose creatinine clearance is less than 70 ml/min or have significant hepatic disease (Aspartate aminotransferase [AST], alanine aminotransferase [ALT], y-GT >2 times upper limit of normal)
13. Patients with thyroid stimulating hormone (TSH) outside normal limits
14. Patients with a history of previous kidney, pancreas or cardiac transplantation
15. Serious or unstable medical or psychological state that may interfere with study participation
16. Patients having taken other systemic investigational drugs (especially for neuropathy) or initiating a new or experimental insulin delivery device within 3 months of starting the study
17. Morbidly obese patients (Body Mass Index [BMI] greater than 40)
18. Patients who refuse to sign the informed consent

Recruitment start date

01/10/2006

Recruitment end date

01/12/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Birmingham
Birmingham
B45 8PF
United Kingdom

Sponsor information

Organisation

University of Birmingham (UK)

Sponsor details

The Medical School
Institute for Biomedical Research
Edgbaston
Birmingham
B45 8PF
United Kingdom
+44 (0)121 414 8162
m.j.stevens@bham.ac.uk

Sponsor type

University/education

Website

http://www.bham.ac.uk/

Funders

Funder type

Government

Funder name

National Institutes of Health (USA)

Alternative name(s)

NIH

Funding Body Type

government organisation

Funding Body Subtype

federal/national government

Location

United States of America

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes