Effects of Pregabalin, Duloxetine & Amitriptyline on Pain & Sleep

Condition(s) targeted: Diabetes Mellitus; Peripheral Neuropathies

Intervention: Pregabalin (Drug); Duloxetine (Drug); Amitriptyline (Drug)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: University of Surrey

Official(s) and/or principal investigator(s):
Professor AN Nicholson, Principal Investigator, Affiliation: University of Surrey
Dr D Kerr, Principal Investigator, Affiliation: Royal Bournemouth Hospital
Dr D Coppini, Principal Investigator, Affiliation: Poole General Hospital

Overall contact:
Professor AN Nicholson, Phone: 01483 683719, Email: A.Nicholson@Surrey.ac.uk

The purpose of this study is 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).

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

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

Primary outcome: Whether there is a reduction in subjective pain as assessed by the Brief Pain Inventory.

Secondary outcome: Whether there has been an improvement in sleep continuity and subjective sleep, morning after cognitive and psychomotor performance, and quality of life (QoL).

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Professor AN Nicholson, Phone: 01483 683719, Email: A.Nicholson@Surrey.ac.uk

Royal Bournemouth Hospital, Bournemouth, Dorset BH7 7DW, United Kingdom; Recruiting
Dr D Kerr, Phone: 01202-704603, Email: David.Kerr@rbch.nhs.uk
D Hill, Phone: 01202 704603, Email: Dawn.Hill@rbch.nhs.uk

Poole General Hospital, Poole, Dorset BH15 2JB, United Kingdom; Recruiting
Dr D Coppini, Phone: 01202 442399, Email: David.Coppini@poole.nhs.uk
P Bowden, Phone: 01202 442399, Email: Paula.Bowden@poole.nhs.uk

University of Surrey Clinical Research Centre, Guildford, Surrey GU2 7XP, United Kingdom; Not yet recruiting
Professor AN Nicholson, Phone: 01483 683719, Email: A.Nicholson@Surrey.ac.uk
Miss J Arthur, Phone: 01483 689788, Email: J.Arthur@Surrey.ac.uk

Starting date: February 2007
Ending date: May 2009
Last updated: February 17, 2009