Official Title: “A Double-Blind, Randomised, Parallel Groups Investigation Into the Effects of Pregabalin, Duloxetine and Amitriptyline on Aspects of Pain, Sleep, and Next Day Performance in Patients Suffering From Diabetic Peripheral Neuropathy”

To assess the effectiveness of pregabalin, duloxetine and amitriptyline compared with placebo in reducing pain in diabetic patients as assessed by Brief Pain Inventory (BPI).

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment

Study Primary Completion Date: December 2008

Little is understood concerning the interaction of pain with sleep. Pain may disrupt sleep leading to daytime sleepiness and poor sleep can increase the perception of pain. There is uncertainty concerning the most effective way in which medication could be used to ease pain and poor sleep in patients such as those with diabetic peripheral neuropathy. Various drugs have been tried or proposed, and these include amitriptyline, pregabalin and duloxetine.

Amitriptyline is believed to relieve pain and improve sleep, though there is little evidence of its beneficial effects on sleep. Furthermore, even at low doses, it affects reaction time, attention, memory, information processing.

In two studies with duloxetine, it has been shown to significantly reduce pain compared with placebo, although little data are available on the usefulness of this compound in the management of pain with poor sleep.

Pregabalin has been shown to be effective in reducing pain, and therefore improving sleep. It has also been demonstrated that it has limited potential to affect daytime cognition. In another study gabapentin (a compound structurally related to pregabalin) demonstrated superior efficacy in the management of pain compared to amitriptyline.

Therefore this study will assess the effectiveness of pregabalin, duloxetine and amitriptyline compared with placebo in reducing pain associated with diabetes and poor sleep.

As the incidence of diabetes is predicted to increase in future years and as a consequence so will the cases of diabetic peripheral neuropathy (DPN), this research will serve to provide essential information on sleep and DPN which will be beneficial now and in the future.

Intervention(s) in this Clinical Trial

• Drug: Pregabalin
• Drug: Duloxetine
• Drug: Amitriptyline

Primary Measures

• Whether there is a reduction in subjective pain as assessed by the Brief Pain Inventory.
  • Time Frame: December 2008
    Safety Issue?: No

Secondary Measures

• Whether there has been an improvement in sleep continuity and subjective sleep, morning after cognitive and psychomotor performance, and quality of life (QoL).
  • Time Frame: December 2008
    Safety Issue?: No

Inclusion Criteria:

• 1. 18 years of age or above
• 2. Have a diagnosis of Diabetes mellitus for at least a year
• 3. Agree not to smoke whilst resident in the CRC
• 4. Able to understand the patient information sheet and provide written informed consent
• 5. Score above 12 on the LANSS
• 6. Have neuropathic pain of diabetic origin
• 7. Score above 25 on MMSE
• 8. Willing to withdraw, under the guidance of their diabetologist, from any current pain medication prior to their first visit to the sleep laboratory. Duration of withdrawal will be at least equivalent to 5 half-lives and will be of a relevant duration given the particular medication used.

Exclusion Criteria:

• 1. There is evidence of an end stage disease of a major system (hepatic, renal, respiratory, haematologic (PA), immunologic, cardiovascular, inflammatory, rheumatology, active infections, peripheral vascular disease, untreated endocrine(hypothyroid)
• 2. There is evidence of a recent ischaemic event
• 3. There is evidence of recurrent and/or severe hypoglycemia requiring assistance in last 3 years
• 4. Evidence of sleep pathology that would interfere with the assessment of treatment (assessed on habituation night)
• 5. Currently receiving treatment for malignancy
• 6. Suffer from seizures including epilepsy
• 7. There is evidence of a history of dependence on or abuse of alcohol/recreational drugs
• 8. Need to use a wheel chair (incompatible with studies in a sleep laboratory)
• 9. Involved in a clinical trial in last 3 months
• 10. Pregnant, lactating or inadequate contraception
• 11. Vision inadequate for the performance tests (as assessed at screening)
• 12. Colour Blind
• 13. Will not co-operate with study procedures
• 14. Will not give permission to inform GP

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Surrey

Overall Clinical Trial Officials and Contacts

Professor AN Nicholson Principal Investigator University of Surrey  

Overall Contact: Professor AN Nicholson 01483 683719 A.Nicholson@Surrey.ac.uk

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00370656

Study ID Number: CRC 235

ClinicalTrials.gov Identifier: NCT00370656

Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency