The Effect of Pregabalin on Pain Related to Walking in Patients With Diabetic Peripheral Neuropathy

Pregabalin (LYRICA®) is a potent and specific ligand at the alpha-2-delta subunit of
voltage-gated calcium channels. It is currently approved for adjunctive therapy for
neuropathic pain conditions. Patients with diabetic peripheral neuropathy suffer from pain in
their feet which interferes with their ability to walk which includes less walking, an
altered gait, and altered balance. At night the peripheral neuropathy also interferes with
their sleep patterns.The hypothesis of this study is that pregabalin, 150 mg bid, will reduce
general daytime pain in patients diagnosed with diabetic peripheral neuropathy and that it
will also reduce the level of pain associated with walking. Consequently, it is hypothesized
that the reduction in pain will result in an increase in the amount of walking they do during
the day, improvements in their gait, balance, risk of falls and sleep patterns.Pain and sleep
quality will be assessed with questionnaires but objective measurements will be used to
assess gait, balance, daytime activities (including walking) and sleep patterns.

Statistical Power Calculations were based on the fact that this is a randomized,
double-blind, placebo-controlled, 2-period crossover study to be conducted at a single site.
Comparisons will be drawn at baseline, at the completion of each 6 weeks of treatment/placebo
arm. The study has been powered at 0.80 for a two-tail analysis with a sensitivity to detect
a 30% delta in pain perception in 40 subjects. From previous studies, the cross-over design
suggested has achieved significance with 20 patients per group. Forty-four patients will be
recruited in total. Significance will be established at an alpha level of 0.05. Both
parametric and non parametric correlations will be carried out between the different
variables measured and progressive logistic regression to determine the relative
contributions of pain relief on the primary and secondary variables being measured in the
study.

Inclusion Criteria:

- Individuals with painful, peripheral neuropathy (ages 40-75 years) and type 2 diabetes
(n=40).

Exclusion Criteria:

- Active ocular or systemic disease

- Recent or recurrent history of musculoskeletal injury,

- Presence of neurological conditions or idiopathic neuropathy

- History of or vertigo

- Use of an aid while walking or difficulty with standing upright

- Visible tremor or uncorrected visual deficits.

- Presence of type 1 diabetes mellitus (defined as C-peptide < 1 ng/ml or diabetes onset
at < 35 years of age in a non-obese patient).

- Presence of diabetic retinopathy that is more severe than "background" level.

- Presence of diabetic nephropathy

- Presence of clinically significant neuropathy that is clearly of non-diabetic origin,
e.g. alcoholic or autoimmune.

- Bilateral amputation of lower extremities or foot ulcers involving the great toes.

- Presence of neuroarthropathy (Charcot deformity) is allowable.

- History of major macrovascular events such as myocardial infarction or stroke within
the past 6 months.

- Patients with moderate or severe hepatic insufficiency or abnormalities of liver
function.

- Presence of significant pedal edema.

- Other serious medical conditions that in the opinion of the investigator, would
compromise the subject's participation in the study.