Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS)
Conditions
Brief summary
The purpose of this study is to determine whether pregabalin is an effective treatment for Chronic Prostatitis/Chronic Pelvic Pain Syndrome.
Detailed description
Primary Objectives 1. To compare six (6) weeks of treatment with pregabalin versus placebo in CP/CPPS participants with respect to the primary endpoint in the NIH-CPSI 2. To evaluate the safety and tolerability of six (6) weeks of pregabalin in CP/CPPS participants Design Eligible participants will receive either pregabalin or placebo, randomly assigned at a ratio of 2:1. Study treatment will be for 6 weeks with dose starting at 150mg going up to 300mg and finally to 600mg daily, to maximum tolerated dose. Participants will be advised to take the study medication 3 times per day. There are 3 clinic visits and 2 telephone contacts. Participants will be offered optional active treatment for an additional 6 weeks at the end of the first 6 weeks. For those participating in both phases there are a total of 4 clinic visits and 5 telephone contacts.
Interventions
DRUGPregabalin
Pregabalin 150 mg/d (50 mg orally 3 times daily) for 2 weeks, then 300 mg/d (100 mg orally 3 times daily) for 2 weeks, and then 600 mg/d (200 mg orally 3 times daily) for 2 weeks.
DRUGPlacebo
Placebo at same frequency as pregabablin
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant has signed and dated the appropriate Informed Consent document. * Participant must have had symptoms of discomfort or pain in the pelvic region for at least a three (3) month period within the last six (6) months.
Exclusion criteria
* Participant has continued evidence of facultative Gram negative or enterococcus with a value of ≥ 1000 and ≤ 100,000 CFU/ml in mid-stream urine (VB2), as demonstrated by repeat culture obtained no less than seven (7) days post antibiotic treatment. * Participant has a calculated creatinine clearance of \<60 mL/min. * Participant has a platelet count \<100,000/mm3. * Participant is allergic to antiepileptic/antiseizure medications. * Participant has a known allergy or sensitivity to pregabalin (Lyrica®). * Participant is taking thiazolidinedione antidiabetic agents (i.e. rosiglitazone and pioglitazone). * Participant has New York Heart Association Class III or IV congestive heart failure. * Participant has a history of thrombocytopenia, or a bleeding diathesis. * Participant has a history of prostate, bladder or urethral cancer. * Participant has a history of alcohol abuse. * Participant has inflammatory bowel disease (such as Crohn's disease or ulcerative colitis, but not irritable bowel syndrome). * Participant has undergone pelvic radiation or systemic chemotherapy. * Participant has undergone intravesical chemotherapy. * Participant has been treated with intravesical BCG. * Participant has unilateral orchalgia without other pelvic symptoms. * Participant has an active urethral stricture. * Participant has a neurological disease or disorder affecting the bladder. * Participant has a neurological impairment or psychiatric disorder preventing his understanding of consent and his ability to comply with the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Decrease in the NIH-CPSI Total Score by at Least 6 Points | Baseline and 6 weeks | Decrease (improvement) in the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) score of at least 6 points from baseline to week 6. The NIH-CPSI measures the 3 key domains of CP/CPPS: pain (location, frequency, and severity; possible score, 0-21), urinary symptoms (irritative and obstructive; possible score, 0-10), and impact/quality of life (possible score, 0-12), for a total possible score of 0 to 43. A 6-point decrease in NIHCPSI score has been shown to be clinically perceptible in previous clinical trials of men with CP/CPPS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Moderately or Markedly Improve on Global Response Assessment (GRA) | 6 weeks | The GRA is a 7-question patient self-reported assessment that measures perception of change in symptoms (improvement, no change, or deterioration). The responses are centered at zero (no change in symptoms). Men who reported that they were moderately or markedly improved on a 7-point GRA at the end of the study were identified as treatment responders. |
| Hospital Anxiety & Depression Scale | 6 weeks | Hospital Anxiety and Depression Scale (HADS) (range, 0-42, with higher scores indicating greater anxiety and depression) |
| Subscales of the NIH-CPSI | 6 weeks | The National Institutes of Health -Chronic Prostatitis Symptom Index (NIH-CPSI) measures the 3 key domains of Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS): pain (location, frequency, and severity; possible score, 0-21), urinary symptoms (irritative and obstructive; possible score, 0-10), and impact/quality of life (possible score, 0-12), for a total possible score of 0 to 43. A higher score indicates more severe symptoms. A 6-point decrease in NIHCPSI score has been shown to be clinically perceptible in previous clinical trials of men with CP/CPPS. |
| Medical Outcomes Study Short Form 12 | 6 weeks | Medical Outcomes Study 12-Item Short Form Health Survey (SF-12) (range, 0-100 for the Physical \[PCS\] and Mental \[MCS\] Component Summary scores, with the mean set at 50 and higher scores indicating better quality of life) |
| Sexual Health Inventory for Men | 6 weeks | Sexual Health Inventory for Men (SHIM) (range, 1-25, with higher scores indicating better sexual function) |
| McGill Pain Questionnaire | 6 weeks | The McGill Pain Questionnaire (MPQ) evaluates the quality of pain as well as the intensity of pain. The McGill Pain Questionnaire ranges from 0-45 for a total pain score, and is the sum of a sensory subscore of 0-33 and affective subscore of 0-12. Higher scores indicate greater pain. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1-Pregabalin Men were randomly assigned to receive pregabalin or placebo in a 2:1 ratio and were treated for 6 weeks. Treatment dosage was escalated as follows: 150 mg/d (50 mg orally 3 times daily) for 2 weeks, then 300 mg/d (100 mg orally 3 times daily) for 2 weeks, and then 600 mg/d (200 mg orally 3 times daily) for 2 weeks. Men assigned to receive placebo underwent a similar escalation in the number of capsules prescribed. | 216 |
| 2-Placebo Men were randomly assigned to receive pregabalin or an identical placebo in a 2:1 ratio and were treated for 6 weeks. Treatment dosage was escalated as follows: 150 mg/d (50 mg orally 3 times daily) for 2 weeks, then 300 mg/d (100 mg orally 3 times daily) for 2 weeks, and then 600 mg/d (200 mg orally 3 times daily) for 2 weeks. Men assigned to receive placebo underwent a similar escalation in the number of capsules prescribed. | 103 |
| Total | 319 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | No longer interested | 2 | 0 |
| Overall Study | Uknown | 3 | 1 |
Baseline characteristics
| Characteristic | Total | 2-Placebo | 1-Pregabalin |
|---|---|---|---|
| Age, Continuous | 47.0 years STANDARD_DEVIATION 13.1 | 45.2 years STANDARD_DEVIATION 12.2 | 48.0 years STANDARD_DEVIATION 13 |
| NIH-CPSI pain subscore (possible score, 0-21) | 12.4 units on a scale STANDARD_DEVIATION 3 | 12.4 units on a scale STANDARD_DEVIATION 3.1 | 12.3 units on a scale STANDARD_DEVIATION 3 |
| NIH-CPSI QOL subscore (possible score, 0-12) | 8.9 units on a scale STANDARD_DEVIATION 2 | 8.9 units on a scale STANDARD_DEVIATION 2 | 8.9 units on a scale STANDARD_DEVIATION 2 |
| NIH-CPSI total score (possible score, 0-43) | 26.1 units on a scale STANDARD_DEVIATION 5.7 | 25.9 units on a scale STANDARD_DEVIATION 6.1 | 26.2 units on a scale STANDARD_DEVIATION 5.6 |
| NIH-CPSI urinary symptoms subscore (possible score, 0-10) | 4.8 units on a scale STANDARD_DEVIATION 2.7 | 4.7 units on a scale STANDARD_DEVIATION 2.7 | 4.9 units on a scale STANDARD_DEVIATION 2.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 38 Participants | 14 Participants | 24 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants | 2 Participants | 11 Participants |
| Race (NIH/OMB) White | 253 Participants | 75 Participants | 178 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 319 Participants | 103 Participants | 216 Participants |
| SF-12 MCS score (possible score, 0-100) | 42.1 units on a scale STANDARD_DEVIATION 10.6 | 42.8 units on a scale STANDARD_DEVIATION 10.6 | 41.8 units on a scale STANDARD_DEVIATION 10.6 |
| SF-12 PCS score (possible score, 0-100) | 44.6 units on a scale STANDARD_DEVIATION 10.2 | 43.9 units on a scale STANDARD_DEVIATION 10.3 | 44.9 units on a scale STANDARD_DEVIATION 10.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 218 | 0 / 106 |
| other Total, other adverse events | 129 / 218 | 62 / 106 |
| serious Total, serious adverse events | 0 / 218 | 0 / 106 |
Outcome results
Primary
Decrease in the NIH-CPSI Total Score by at Least 6 Points
Decrease (improvement) in the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) score of at least 6 points from baseline to week 6. The NIH-CPSI measures the 3 key domains of CP/CPPS: pain (location, frequency, and severity; possible score, 0-21), urinary symptoms (irritative and obstructive; possible score, 0-10), and impact/quality of life (possible score, 0-12), for a total possible score of 0 to 43. A 6-point decrease in NIHCPSI score has been shown to be clinically perceptible in previous clinical trials of men with CP/CPPS.
Time frame: Baseline and 6 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1-Pregabalin | Decrease in the NIH-CPSI Total Score by at Least 6 Points | 103 Participants |
| 2-Placebo | Decrease in the NIH-CPSI Total Score by at Least 6 Points | 38 Participants |
Secondary
Hospital Anxiety & Depression Scale
Hospital Anxiety and Depression Scale (HADS) (range, 0-42, with higher scores indicating greater anxiety and depression)
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1-Pregabalin | Hospital Anxiety & Depression Scale | 12.4 units on a scale | Standard Deviation 7.8 |
| 2-Placebo | Hospital Anxiety & Depression Scale | 12.2 units on a scale | Standard Deviation 7.8 |
Secondary
McGill Pain Questionnaire
The McGill Pain Questionnaire (MPQ) evaluates the quality of pain as well as the intensity of pain. The McGill Pain Questionnaire ranges from 0-45 for a total pain score, and is the sum of a sensory subscore of 0-33 and affective subscore of 0-12. Higher scores indicate greater pain.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1-Pregabalin | McGill Pain Questionnaire | 9.6 units on a scale | Standard Deviation 8.8 |
| 2-Placebo | McGill Pain Questionnaire | 12.4 units on a scale | Standard Deviation 9.1 |
Secondary
Medical Outcomes Study Short Form 12
Medical Outcomes Study 12-Item Short Form Health Survey (SF-12) (range, 0-100 for the Physical \[PCS\] and Mental \[MCS\] Component Summary scores, with the mean set at 50 and higher scores indicating better quality of life)
Time frame: 6 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1-Pregabalin | Medical Outcomes Study Short Form 12 | Physical [PCS] Component Summary | 46.9 units on a scale | Standard Deviation 10.1 |
| 1-Pregabalin | Medical Outcomes Study Short Form 12 | Mental [MCS] Component Summary | 45.0 units on a scale | Standard Deviation 11.2 |
| 2-Placebo | Medical Outcomes Study Short Form 12 | Physical [PCS] Component Summary | 44.3 units on a scale | Standard Deviation 10.6 |
| 2-Placebo | Medical Outcomes Study Short Form 12 | Mental [MCS] Component Summary | 44.6 units on a scale | Standard Deviation 10.6 |
Secondary
Moderately or Markedly Improve on Global Response Assessment (GRA)
The GRA is a 7-question patient self-reported assessment that measures perception of change in symptoms (improvement, no change, or deterioration). The responses are centered at zero (no change in symptoms). Men who reported that they were moderately or markedly improved on a 7-point GRA at the end of the study were identified as treatment responders.
Time frame: 6 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1-Pregabalin | Moderately or Markedly Improve on Global Response Assessment (GRA) | 68 Participants |
| 2-Placebo | Moderately or Markedly Improve on Global Response Assessment (GRA) | 20 Participants |
Secondary
Sexual Health Inventory for Men
Sexual Health Inventory for Men (SHIM) (range, 1-25, with higher scores indicating better sexual function)
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1-Pregabalin | Sexual Health Inventory for Men | 16.4 units on a scale | Standard Deviation 8.4 |
| 2-Placebo | Sexual Health Inventory for Men | 17.2 units on a scale | Standard Deviation 7.8 |
Secondary
Subscales of the NIH-CPSI
The National Institutes of Health -Chronic Prostatitis Symptom Index (NIH-CPSI) measures the 3 key domains of Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS): pain (location, frequency, and severity; possible score, 0-21), urinary symptoms (irritative and obstructive; possible score, 0-10), and impact/quality of life (possible score, 0-12), for a total possible score of 0 to 43. A higher score indicates more severe symptoms. A 6-point decrease in NIHCPSI score has been shown to be clinically perceptible in previous clinical trials of men with CP/CPPS.
Time frame: 6 weeks
Population: The overall number of participants analyzed in the secondary outcome measures were 210 for the pregabalin arm and 103 for the placebo arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1-Pregabalin | Subscales of the NIH-CPSI | Total score | 19.7 units on the NIH-CPSI scale | Standard Deviation 8.5 |
| 1-Pregabalin | Subscales of the NIH-CPSI | Pain domain score | 9.1 units on the NIH-CPSI scale | Standard Deviation 3.1 |
| 1-Pregabalin | Subscales of the NIH-CPSI | Urinary symptoms domain score | 3.7 units on the NIH-CPSI scale | Standard Deviation 2.6 |
| 1-Pregabalin | Subscales of the NIH-CPSI | Quality of life domain | 6.9 units on the NIH-CPSI scale | Standard Deviation 2.9 |
| 2-Placebo | Subscales of the NIH-CPSI | Quality of life domain | 7.4 units on the NIH-CPSI scale | Standard Deviation 3.1 |
| 2-Placebo | Subscales of the NIH-CPSI | Total score | 21.6 units on the NIH-CPSI scale | Standard Deviation 8.9 |
| 2-Placebo | Subscales of the NIH-CPSI | Urinary symptoms domain score | 4.0 units on the NIH-CPSI scale | Standard Deviation 2.7 |
| 2-Placebo | Subscales of the NIH-CPSI | Pain domain score | 10.1 units on the NIH-CPSI scale | Standard Deviation 4.7 |