Efficacy of Pregabalin and Duloxetine in Patients With PDPN: the Effect of Pain on Cognitive Function, Sleep and Quality of Life (BLOSSOM)
Painful Diabetic Peripheral Neuropathy
About this trial
This is an interventional treatment trial for Painful Diabetic Peripheral Neuropathy
Eligibility Criteria
Inclusion Criteria:
- Female and male patients aged 18-85 years.
- Patients with a history of type 2 diabetes mellitus according to The American Diabetes Association (ADA).
- Patients with a diagnosis of painful diabetic peripheral neuropathy (PDPN) caused by type 2 diabetes mellitus based on DN4 ≥4.
- Patients whose average pain intensity in PDPN in last 24 hours (measured by VAS), evaluated on baseline visit, is equal or more than 40 mm (0 mm ='no pain' and 100 mm ='worst possible pain').
- Ability to adhere to trial protocol.
- Written informed consent.
The methods for inclusion criteria assessment include medical history, interview, completing the DN4 questionnaire, physical examination, assesment of pain on VAS and laboratory analyses.
Exclusion Criteria:
- Patients who took PDPN medication and/or analgesics on a day of baseline visit.
- Patients with a known hypersensitivity to duloxetine, pregabalin, paracetamol or tramadol or any of the inactive ingredients or have any contraindication for the use of duloxetine, pregabalin, paracetamol or tramadol.
Patients with a history of inadequate pain response (pain reduced was equal or less than 30%) to:
3.1. pregabalin at maximum allowed treatment daily dose 600 mg, 3.2. duloxetine at maximum allowed treatment daily dose 120 mg, 3.3. venlafaxine at maximum allowed treatment daily dose 375 mg, 3.4. gabapentin on daily treatment dose more than 1800 mg 3.5. amitriptilin at maximum allowed treatment daily dose 150 mg.
Patients, who are currently treated with a daily dose that exceeds:
4.1. 150 mg of pregabalin, 4.2. 60 mg of duloxetine, 4.3. 150 mg of venlafaxine, 4.4. 600 mg of gabapentin.
- Patients with an uncontrolled type 2 diabetes mellitus.
- The average scores of less than 20 on MoCA.
- Have any other type of neuropatic pain, contrasted to PDPN.
- Evidence of another cause of distal polyneuropathy other than diabetic.
- Have a serious (evaluated by physician) unstable cardiovascular (e.g. uncontrolled hypertension), hepatic, renal, respiratory, ophthalmologic, gastrointestinal, or hematologic illness, symptomatic peripheral vascular disease, malignant disease or other medical condition that could lead to hospitalisation during the course of the trial.
- Have a diagnosis or history of uncontrolled glaucoma.
- Known or suspected alcohol or drug abuse or addiction (excluding nicotine and caffeine).
- Patients with a history of depression (less than one year after completing the last medical treatment), mania, bipolar disorder, psychosis or schizophrenia.
- Pregnancy, lactation and women of child-bearing potential without highly effective* or at least acceptable** contraception (according to the Recommendations related to contraception and pregnancy testing in clinical trials).
- Patients with a history of epilepsy, stroke or neurodegenerative disease.
- Patients taking Monoamine oxidase (MAO) inhibitors or are within one year of their withdrawal.
- Acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C).
- Patients with suspected Restless leg syndrome (RLS).
- Abnormal thyroid-stimulating hormone (TSH) concentrations (according to the references value of the local laboratory).
- Vitamin B12 and folic acid deficiency (according to the reference values of the local laboratory).
- Surgical procedures planned to occur during trial (patients may be rescreened following completion of and recovery from the surgical procedure).
- Concomitant treatment that might influence the final therapeutic effect of the tested active substances including non-medical treatments.
Patients who under the opinion of the investigator will not be compliant to the treatment or not be able to finish the trial for any other reason.
Highly effective contraception is:
- combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation(oral, intravaginal, transdermal)
- progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
- intrauterine device (IUD)
- intrauterine hormone-releasing system (IUS)
- bilateral tubal occlusion
- vasectomised partner
sexual abstinence
**Acceptable contraception is:
- progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action
- male or female condom with or without spermicide
- cap, diaphragm or sponge with spermicide
Sites / Locations
- Opća bolnica Karlovac
- Clinical Medical Center Osijek
- KB Merkur, Sveučilišna klinika Vuk Vrhovac
- Klinička bolnica Sveti Duh
- JZU Univerzitetska klinika za endokrinologija, dijabetes I metabolicki bolesti - Skopje
- JZU Univerzitetska klinika za nevrologija
- Gabinet Neurologiczny, prof. Adam Stępień
- Poradnia neurologiczna, Centrum terapii dzieci i Dorosłych FIMEDICA Sp. z o.o.
- Klinički centar Srbije
- Klinički centar Niš
- Klinički centar Vojvodine
- Zdravstveni dom Koper
- Clemenz Marjetka - Nevrološka Ordinacija
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Pregabalin Krka Arm
Dulsevia® Arm
ARM 1: pregabalin (Pregabalin Krka 25-150 mg/ day) FLEXIBLE-DOSE REGIMEN. Investigator can choose on V2: Total Pregabalin Krka daily dose: 25 mg/day Total Pregabalin Krka daily dose: 50 mg/day Total Pregabalin Krka daily dose: 75 mg/day Total Pregabalin Krka daily dose: 150 mg/day Total Pregabalin Krka daily dose: 300 mg/day (from Phone call 1 further on) V3: daily dose should be achieved: MINIMUM dose 150 mg/day Investigator can choose: total Pregabalin Krka daily dose 150 mg/day or 300 mg/day or 600 mg/day Investigator can choose: total Pregabalin Krka daily dose 150 mg/day or 300 mg/day or 600 mg/day V4: Investigator can choose: total Pregabalin Krka daily dose 150 mg/day or 300 mg/day or 600 mg/day
• ARM 2: duloxetine (Dulsevia® 30-60 mg/ day) FLEXIBLE-DOSE REGIMEN: Investigator can choose on V2: Total Dulsevia® daily dose: 30 mg/day Total Dulsevia® daily dose: 60 mg/day V3: daily dose should be achieved: MINIMUM dose 60 mg/day Investigator can choose total Dulsevia® daily dose 60 mg/day or 90 mg/day or 120 mg/day. V4: Investigator can choose total Dulsevia® daily dose 60 mg/day or 90 mg/day or 120 mg/day.