Trial Outcomes & Findings for A Randomized Double-Blind Study Testing the Effects of Pregabalin on Diabetic Neuropathy (NCT NCT00573261)

NCT ID: NCT00573261

Last Updated: 2014-07-21

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

40 participants

Primary outcome timeframe

baseline and at end of a 4-week intervention

Results posted on

2014-07-21

Participant Flow

Subjects were recruited from the outpatient endocrine clinics of a tertiary academic center and locally via advertisement between March 3, 2006 and April 1, 2008.

There were 4 subjects who provided study consent but did not complete the baseline assessment because of unwillingness to wear the LifeShirt monitor (n=2 in placebo arm) and inability of keeping baseline assessment appointment due to job reassignment (n=2 in pregabalin arm).

Participant milestones

Participant milestones
Measure	Placebo Placebo Placebo : Subjects will take placebo for the duration of four weeks. The dosage will range from 75 mg twice a day to 300 mg twice a day.	Pregabalin Pregabalin medication Pregabalin : Subjects will take pregabalin for the duration of four weeks. The dosage will range from 75 mg twice a day to 300 mg twice a day.
Overall Study STARTED	20	20
Overall Study COMPLETED	14	15
Overall Study NOT COMPLETED	6	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Randomized Double-Blind Study Testing the Effects of Pregabalin on Diabetic Neuropathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pregabalin n=20 Participants Pregabalin medication Pregabalin : Subjects will take pregabalin for the duration of four weeks. The dosage will range from 75 mg twice a day to 300 mg twice a day.	Placebo n=20 Participants Placebo Placebo : Subjects will take placebo for the duration of four weeks. The dosage will range from 75 mg twice a day to 300 mg twice a day.	Total n=40 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants	13 Participants n=7 Participants	29 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Age, Continuous	55.1 years STANDARD_DEVIATION 14.36 • n=5 Participants	59.65 years STANDARD_DEVIATION 12.5 • n=7 Participants	57.4 years STANDARD_DEVIATION 13.5 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	14 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants	20 participants n=7 Participants	40 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and at end of a 4-week intervention

Population: A data card failure of the baseline heart rate record with the VivoMetrics system occurred for one subject who had completed baseline and 4-week assessments, leaving 28 subjects (n=13 in placebo, n=15 in pregabalin)having both completed baseline and end of 4-week R-R intervals for heart rate variability analysis.

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Placebo	Pregabalin n=15 Participants Pregabalin
Assessing the Change in Resting Blood Pressure Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy. Systolic Blood Pressure (mm Hg)	-7.63 mm Hg Standard Deviation 10.46	-8.98 mm Hg Standard Deviation 17.61
Assessing the Change in Resting Blood Pressure Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy. Diastolic Blood Pressure (mm Hg)	-4.41 mm Hg Standard Deviation 7.79	-4.93 mm Hg Standard Deviation 8.64

PRIMARY outcome

Timeframe: baseline and at end of a 4-week intervention

The LifeShirt System, developed by VivoMetrics, is a lightweight vest with embedded sensors that continuously collect information on a range of cardiopulmonary parameters. It was used to collect and store the respiratory rate, posture, activity level, QRS complexes, and R-R intervals via a 3-axis accelerometer and a 3-lead, single channel electrocardiogram.

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Placebo	Pregabalin n=15 Participants Pregabalin
Assessing the Change in Heart Rate by Means of the LifeShirt System Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy.	-2.94 Beats Per Minute Standard Deviation 6.96	-3.49 Beats Per Minute Standard Deviation 5.51

PRIMARY outcome

Timeframe: baseline and at end of a 4-week intervention

Heart rate variability parameters generated by the frequency domain analysis included: total power (area under the curve) over all frequencies, very low frequency (VLF, 0-0.04 Hz),low frequency (LF, 0.04-0.15 Hz), and high frequency (HF,0.15-0.4 Hz).

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Placebo	Pregabalin n=15 Participants Pregabalin
Assessing the Change in Heart Rate Variability by Means of the LifeShirt System Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy. Total Power	45.29 Hertz (Hz) Standard Deviation 418.09	-140.99 Hertz (Hz) Standard Deviation 629.81
Assessing the Change in Heart Rate Variability by Means of the LifeShirt System Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy. Low Frequency	32.41 Hertz (Hz) Standard Deviation 229.51	-67.06 Hertz (Hz) Standard Deviation 252.06
Assessing the Change in Heart Rate Variability by Means of the LifeShirt System Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy. High Frequency	-12.19 Hertz (Hz) Standard Deviation 79.91	-41.37 Hertz (Hz) Standard Deviation 175.89

PRIMARY outcome

Timeframe: baseline and at end of a 4-week intervention

Heart Rate Variability parameters generated by the frequency domain analysis included: Low Frequency / High Frequency (LF/HF), as well as normalized LF (normalized LF=LF/\[total power-VLF\]) and normalized HF (normalized HF=HF/\[total power-VLF\]).

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Placebo	Pregabalin n=15 Participants Pregabalin
Assessing the Change in Heart Rate Variability by Means of the LifeShirt System Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy. Low frequency/High frequency	0.37 Ratio Standard Deviation 0.33	-1.30 Ratio Standard Deviation 2.89
Assessing the Change in Heart Rate Variability by Means of the LifeShirt System Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy. Normalized low frequency	0.0066 Ratio Standard Deviation 0.023	-0.049 Ratio Standard Deviation 0.092
Assessing the Change in Heart Rate Variability by Means of the LifeShirt System Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy. Normalized high frequency	-0.038 Ratio Standard Deviation 0.066	0.039 Ratio Standard Deviation 0.094

PRIMARY outcome

Timeframe: baseline and at end of a 4-week intervention

Heart rate variability parameters yielded by time domain analysis included the mean of all R-R intervals (ANN), standard deviation of all R-R intervals (SDNN), root mean square of successive differences (RMSSD), and standard deviation of the averages of R-R intervals for all 5-minute segments within the block (SDANN).

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Placebo	Pregabalin n=15 Participants Pregabalin
Assessing the Change of Parameters of Autonomic Nerve Function Such as Heart Rate Variability by Means of the LifeShirt System Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy. ANN	21.47 milliseconds Standard Deviation 84.56	65.44 milliseconds Standard Deviation 108.95
Assessing the Change of Parameters of Autonomic Nerve Function Such as Heart Rate Variability by Means of the LifeShirt System Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy. SDNN	3.42 milliseconds Standard Deviation 8.83	-0.55 milliseconds Standard Deviation 20.03
Assessing the Change of Parameters of Autonomic Nerve Function Such as Heart Rate Variability by Means of the LifeShirt System Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy. SDANN	0.68 milliseconds Standard Deviation 7.67	1.38 milliseconds Standard Deviation 12.16
Assessing the Change of Parameters of Autonomic Nerve Function Such as Heart Rate Variability by Means of the LifeShirt System Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy. RMSSD	0.58 milliseconds Standard Deviation 12.94	-0.51 milliseconds Standard Deviation 8.44

PRIMARY outcome

Timeframe: baseline and at end of a 4-week intervention

Heart rate variability parameters yielded by time domain analysis included the number of N-N intervals that differ by more than 50 milliseconds from adjacent intervals divided by the total number of all N-N intervals (pNN50).

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Placebo	Pregabalin n=15 Participants Pregabalin
Assessing the Change of Parameters of Autonomic Nerve Function Such as Heart Rate Variability by Means of the LifeShirt System Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy.	15.97 Intervals more than 50 ms Standard Deviation 92.66	-2.25 Intervals more than 50 ms Standard Deviation 41.81

PRIMARY outcome

Timeframe: baseline and at end of a 4-week intervention

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Placebo	Pregabalin n=15 Participants Pregabalin
Assessing the Change of Parameters of Autonomic Nerve Function Such as Heart Rate Variability by Means of the LifeShirt System Upon Treatment of Pregabalin vs. Placebo in Patients With Diabetes and Peripheral Neuropathy.	0.011 Ratio Standard Deviation 0.087	0.0015 Ratio Standard Deviation 0.051

SECONDARY outcome

Timeframe: baseline and end of 4 week intervention

Population: A data card failure of the baseline heart rate record with the VivoMetrics system occurred for one subject who had completed baseline and their 4-week assessments, leaving 28 subjects (n=13 in placebo, n=15 in pregabalin)having both completed baseline and end of 4-week R-R intervals for heart rate variability analysis.

Pain severity was evaluated using the Visual Analog Scale, the Modified Brief Pain Inventory-Short Form, and the Neuropathy Pain Scale. The Visual Analog Scale was scored within a range of 0-100 with 0=no pain and 100=the worst imaginable pain. The Brief Pain Inventory is made up of two parts: total pain and pain interference. The total pain score is the sum of most, least, average, and now pain scored within a range of 0-10 with 0=no pain and 10=pain as bad as you can imagine. The pain interference score is the sum of affective and activity interference - how pain interfered with general activity, mood, walking ability, normal work, relationships, sleep, and enjoyment of life. It was scored within a range of 0-10 with 0=pain does not interfere and 10=pain completely interferes. The Neuropathy Pain Scale total is the sum of 10 items -cold, sharp, deep, dull, hot, intense, itchy, sensitive, surface, and unpleasant pain scored within a range of 0-10 with 0=no pain and 10=most pain.

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Placebo	Pregabalin n=15 Participants Pregabalin
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Visual analog pain rating	-21.29 units on a scale Standard Deviation 35.62	-43.27 units on a scale Standard Deviation 32.03
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Brief pain inventory - Total Pain	-1.36 units on a scale Standard Deviation 9.01	-9.13 units on a scale Standard Deviation 9.63
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Brief pain inventory - Most Pain	-1.07 units on a scale Standard Deviation 3.69	-3.33 units on a scale Standard Deviation 3.46
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Brief pain inventory - Least Pain	-0.071 units on a scale Standard Deviation 1.54	-1.20 units on a scale Standard Deviation 1.93
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Brief pain inventory - Average Pain	-0.64 units on a scale Standard Deviation 2.79	-2.87 units on a scale Standard Deviation 3.04
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Brief pain inventory - Now pain	0.43 units on a scale Standard Deviation 1.95	-1.73 units on a scale Standard Deviation 2.55
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Pain interference	-1.43 units on a scale Standard Deviation 7.54	-13.93 units on a scale Standard Deviation 10.35
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Affective interference	-0.071 units on a scale Standard Deviation 3.69	-5.27 units on a scale Standard Deviation 5.71
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Activity Interference	-1.36 units on a scale Standard Deviation 4.94	-8.67 units on a scale Standard Deviation 7.03
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Neuropathy pain scale (total)	-10.31 units on a scale Standard Deviation 11.15	-27.33 units on a scale Standard Deviation 22.95
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Cold pain	-1.23 units on a scale Standard Deviation 3.37	-2.13 units on a scale Standard Deviation 3.85
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Sharp pain	-0.92 units on a scale Standard Deviation 2.40	-2.53 units on a scale Standard Deviation 4.16
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Deep pain	-0.23 units on a scale Standard Deviation 3.54	-3.00 units on a scale Standard Deviation 3.51
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Dull pain	0 units on a scale Standard Deviation 2.38	-2.07 units on a scale Standard Deviation 3.75
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Hot pain	-1.77 units on a scale Standard Deviation 4.07	-2.53 units on a scale Standard Deviation 3.40
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Intense pain	-1.38 units on a scale Standard Deviation 1.66	-3.13 units on a scale Standard Deviation 3.09
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Itchy pain	0 units on a scale Standard Deviation 2.08	-4.07 units on a scale Standard Deviation 3.92
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Sensitive pain	-2.31 units on a scale Standard Deviation 3.07	-1.60 units on a scale Standard Deviation 3.11
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Surface pain	-1.46 units on a scale Standard Deviation 1.56	-3.20 units on a scale Standard Deviation 3.19
To Assess the Change of Pain Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Unpleasant pain	-1.00 units on a scale Standard Deviation 2.38	-3.07 units on a scale Standard Deviation 3.52

SECONDARY outcome

Timeframe: baseline and at end of a 4-week intervention

Anxiety symptoms were measured using the Spielberger State-Trait Anxiety Inventory Scale (STAI) for symptoms of anxiety. State anxiety: score range, 20-80 (higher score=greater levels of state anxiety). Trait anxiety: score range, 20-80 (higher score=greater levels of trait anxiety).

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Placebo	Pregabalin n=15 Participants Pregabalin
To Assess the Change of Anxiety Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. State Anxiety	0.57 units on a scale Standard Deviation 5.91	1.2 units on a scale Standard Deviation 3.28
To Assess the Change of Anxiety Symptoms Upon Treatment of Pregabalin in Comparison to Placebo. Trait Anxiety	1 units on a scale Standard Deviation 6.16	-3.67 units on a scale Standard Deviation 5.51

SECONDARY outcome

Timeframe: baseline and at end of a 4-week intervention

The Beck Depression Inventory Scale measures symptoms of depression, score range, 0-63 (higher score=greater severity of depressive symptoms)

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Placebo	Pregabalin n=15 Participants Pregabalin
To Assess the Change of Depressive Symptoms Upon Treatment of Pregabalin in Comparison to Placebo.	1.21 units on a scale Standard Deviation 4.25	-1.20 units on a scale Standard Deviation 1.57

SECONDARY outcome

Timeframe: baseline and at end of a 4-week intervention

The Sheehan Disability Scale was used to evaluate functional impairment in work/school, social and family life, score range, 0-10; the 3 items can be summed into a single dimensional measure of global functional impairment that ranges from 0(unimpaired) to 30 (highly impaired).

Outcome measures

Outcome measures
Measure	Placebo n=13 Participants Placebo	Pregabalin n=15 Participants Pregabalin
To Assess the Change in Disability Scale Upon Treatment of Pregabalin in Comparison to Placebo. Disability scale - Global functioning score	-1.67 units on a scale Standard Deviation 4.64	-7.73 units on a scale Standard Deviation 7.70
To Assess the Change in Disability Scale Upon Treatment of Pregabalin in Comparison to Placebo. Disability scale - Work/school disability	-0.42 units on a scale Standard Deviation 1.93	-2.93 units on a scale Standard Deviation 3.26
To Assess the Change in Disability Scale Upon Treatment of Pregabalin in Comparison to Placebo. Disability scale - Social disability	-0.58 units on a scale Standard Deviation 1.73	-2.13 units on a scale Standard Deviation 2.83
To Assess the Change in Disability Scale Upon Treatment of Pregabalin in Comparison to Placebo. Disability scale - Family disability	-0.67 units on a scale Standard Deviation 1.92	-2.67 units on a scale Standard Deviation 3.02

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Pregabalin

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=14 participants at risk Placebo Placebo : Subjects will take placebo for the duration of four weeks. The dosage will range from 75 mg twice a day to 300 mg twice a day.	Pregabalin n=15 participants at risk Pregabalin medication Pregabalin : Subjects will take pregabalin for the duration of four weeks. The dosage will range from 75 mg twice a day to 300 mg twice a day.
General disorders Dizziness	0.00% 0/14 • Participants were contacted by phone starting at the end of week 1 for potential adverse effects and titration of the study drug throughout 4-week treatment period.	13.3% 2/15 • Number of events 2 • Participants were contacted by phone starting at the end of week 1 for potential adverse effects and titration of the study drug throughout 4-week treatment period.
General disorders Swelling of the lower extremities	0.00% 0/14 • Participants were contacted by phone starting at the end of week 1 for potential adverse effects and titration of the study drug throughout 4-week treatment period.	6.7% 1/15 • Number of events 1 • Participants were contacted by phone starting at the end of week 1 for potential adverse effects and titration of the study drug throughout 4-week treatment period.

Additional Information

Dr. Wei Jiang

Duke University Medical Center

Phone: 919-668-0762

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place