Trazodone in Painful Diabetic Neuropathy

NCT03202979 | Completed Phase 2

• 2 other identifiers: 039(B)PO161432016-002772-27
• Study Type: interventional
• Target: 142
• Locations: 3 countries
• Sites: 20

Brief Summary

The aim of the study is to collect preliminary information on the effect of low doses of trazodone on pain intensity in patients with painful diabetic neuropathy and to evaluate the neuropathic pain symptoms, anxiety, sleep, quality of life, safety and tolerability.

Conditions

Painful Diabetic Neuropathy

Keywords

Trazodone; Placebo; Gabapentin; Neuropathic pain

Outcome Measures

Primary Outcomes (1)

• Change of item 5 score in Brief Pain Inventory Short Form (BPI-SF) scale

  Change from baseline of item 5 score in BPI-SF numering scale after 56 days.

  Baseline - Day 56

Secondary Outcomes (13)

• Change of item 5 score in Brief Pain Inventory Short Form (BPI-SF) scale

  Baseline - Days 7, 14, 21, 28, 35, 42, 49, 63

• Change of item 3 score in Brief Pain Inventory Short Form (BPI-SF) scale

  Baseline - Days 7, 14, 21, 28, 35, 42, 49, 56 and 63.

• Change of item 4 score in Brief Pain Inventory Short Form (BPI-SF) scale

  Baseline - Days 7, 14, 21, 28, 35, 42, 49, 56 and 63.

• Change of item 5 score in Brief Pain Inventory Short Form (BPI-SF) scale

  Baseline - Days 7, 14, 21, 28, 35, 42, 49, 56 and 63.

• Change of item 6 score in Brief Pain Inventory Short Form (BPI-SF) scale

  Baseline - Days 7, 14, 21, 28, 35, 42, 49, 56 and 63.

Study Arms (3)

Group 1

EXPERIMENTAL

Trazodone 20 mg

Drug: Trazodone 20 mg

Group 2

EXPERIMENTAL

Trazodone 10 mg

Drug: Trazodone 10 mg

Group 3

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Trazodone 20 mg DRUG

Oral administration of trazodone 20 mg (corresponding to 10 drops of trazodone hydrochloride 6% oral solution), three times a day, for 8 weeks. Trazodone total daily dose: 60 mg. After the 8-week treatment period, patients will receive trazodone 10 mg (corresponding to 5 drops of trazodone hydrochloride 6% oral solution) three times a day for 1-week tapering period in double blind conditions.

Also known as: Trittico®

Group 1

Trazodone 10 mg DRUG

Oral administration of trazodone 10 mg (corresponding to 5 drops of trazodone hydrochloride 6% oral solution), three times a day, for 8 weeks. Trazodone total daily dose: 30 mg. In order to maintain the study double-blind conditions,patients randomized in this group will be co-administered with placebo oral solution (5 drops). After the 8-week treatment period, patients will receive placebo oral solution three times a day for 1-week tapering period in double blind conditions.

Also known as: Trittico®

Group 2

Placebo DRUG

Oral administration of placebo oral solution (10 drops) three times a day, for 8-week treatment. After the 8-week treatment period, patients will receive placebo oral solution three times a day for 1-week tapering period in double blind conditions.

Group 3

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patient of any ethnic origin between 18 and 75 years of age (limits included).
• Patient with painful diabetic symmetric polyneuropathy manifesting with distally distributed neuropathic pain.
• Stable glycaemic control with a value of HbA1c ≤ 10% at Screening Visit.
• Pain persisting for at least 3 months.
• Neuropathic pain confirmed by DN4 score ≥ 4 at Screening Visit.
• BPI-SF 24-hour average pain score (item 5) ≥ 4 at Screening Visit and Baseline Visit.
• Patient who is currently not receiving treatment for diabetic neuropathic pain or patient who is receiving treatment, with drug/s other than gabapentin, and have completed the required washout.
• Women of childbearing potential must have a negative pregnancy test at Screening Visit and have to agree not to start a pregnancy from the signature of the informed consent up to thirty days after the last administration of the investigational product, using an appropriate birth control method, such as combined estrogen and progestogen containing hormonal contraception (e.g. oral, intravaginal, transdermal), progestogen-only hormonal contraception (e.g. oral, injectable, implantable), intrauterine device (IUD) or intrauterine hormone- releasing system (IUS) in combination with male condom, bilateral tubal occlusion, vasectomised partner, sexual abstinence.
• Legally capable to give their consent to participate in the study and available to sign and date the written informed consent.

You may not qualify if:

• Known hypersensitivity to trazodone or gabapentin or their excipients.
• Other forms of neuropathic pain or non-neuropathic pain (included but not limited to peripheral arterial disease, radiculopathy, mononeuropathy, proximal motor neuropathy, post-operative pain, etc).
• Concomitant treatment with other medications for pain management.
• Concomitant treatment with potent CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, indinavir) or drugs known to prolong QT interval.
• Use of trazodone or gabapentin in the previous 3 months.
• Clinically significant abnormalities on physical examination, vital signs, ECG, laboratory tests at Screening Visit that in the opinion of Investigator would compromise patient's participation in the study.
• Active foot ulcer or previous major limb amputation.
• Myocardial infarction or angioplasty or by-pass graft procedures within the past 6 months.
• Patient with increased risk of Torsade de Pointes (e.g. family history of long QT syndrome) or QTcF value higher than 450 msec (male) and QTcF value higher than 470 msec (female) at Screening Visit.
• Transient ischemic attack or cerebral vascular accident within the past 6 months.
• GFR value \< 60 ml/min calculated with MDRD formula.
• Significant liver disease, defined as known active hepatitis or elevated liver enzymes over 3 fold the upper normal limit of laboratory normal ranges.
• Patient with latent or known hereditary problems of galactose intolerance or the Lapp lactase deficiency or glucose-galactose malabsorption.
• Positive urine drug screen for CNS active drugs (cocaine, opioids, amphetamines and cannabinoids) a Screening Visit.
• Positive present history of glaucoma.

Sponsors & Collaborators

• Aziende Chimiche Riunite Angelini Francesco S.p.A: lead
• Chiltern International Inc.: collaborator

Study Sites (20)

NEUROHK s.r.o.

Choceň, 565 01, Czechia

Location

Litnea s.r.o. Neurologicka ambulance

Litoměřice, 412 01, Czechia

Location

Neurosanatio s.r.o.

Litomyšl, 570 01, Czechia

Location

MP-neuro s.r.o. Poliklinika Modry pavilon

Ostrava, 710 00, Czechia

Location

Nemocnice Pardubickeho kraje a.s. Pardubicka nemocnice Neurologická klinika

Pardubice, 532 03, Czechia

Location

Diabetologicka ambulance Milan Kvapil s.r.o.

Prague, 149 00, Czechia

Location

Vestra Clinics s.r.o.

Rychnov Nad Knežnou, 516 01, Czechia

Location

Budai Irgalmasrendi Korhaz Belgyógyászati Centrum

Budapest, 1027, Hungary

Location

Semmelweis Egyetem AOK I. sz. Belgyogyaszati Klinika

Budapest, 1083, Hungary

Location

Markhot Ferenc Oktatokorhaz es Rendelointezet Diabetesz Gondozo

Eger, 3300, Hungary

Location

Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaz I. sz. Belgyogyaszati Osztaly

Gyula, 5700, Hungary

Location

Bacs-Kiskun Megyei Korhaz II. sz. Belgyogyaszati Osztaly

Kecskemét, 6000, Hungary

Location

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont I. Sz. Belgyogyaszati Klinika

Szeged, 6720, Hungary

Location

Silmedic Sp. z o.o.

Katowice, 40-282, Poland

Location

Pro Familia Altera Sp. z o.o.

Katowice, 40-648, Poland

Location

NZOZ Neuromed M. i M. Nastaj Sp. P.

Lublin, 20-064, Poland

Location

RCMed Oddział Sochaczew

Sochaczew, 96-500, Poland

Location

Jeka Sławomir Niepubliczny Zakład Opieki Zdrowotnej "Nasz Lekarz" Praktyka Grupowa Lekarzy Rodzinnych z Przychodnia Specjalistyczna

Torun, 87-100, Poland

Location

NBR Polska Tomasz Klodawski

Warsaw, 00-465, Poland

Location

Medycyna Kliniczna

Warsaw, 00-660, Poland

Location

Related Publications (1)

• Lipone P, Ehler E, Nastaj M, Palka-Kisielowska I, Cruccu G, Truini A, Di Loreto G, Del Vecchio A, Pochiero I, Comandini A, Calisti F, Cattaneo A. Efficacy and Safety of Low Doses of Trazodone in Patients Affected by Painful Diabetic Neuropathy and Treated with Gabapentin: A Randomized Controlled Pilot Study. CNS Drugs. 2020 Nov;34(11):1177-1189. doi: 10.1007/s40263-020-00760-2.

  PMID: 32936427 DERIVED

Related Links

• Sponsor's website

MeSH Terms

Conditions

Diabetic Neuropathies; Neuralgia

Interventions

Trazodone

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyridones; Pyridines

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The present study will be performed in double blind conditions. During the study, neither the Investigator nor the patient will be aware of the treatment assigned.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-blind, placebo controlled, double-dummy, dose finding, multicentre, international, prospective, pilot study.

Study Record Dates

• First Submitted: June 23, 2017
• First Posted: June 29, 2017
• Study Start: May 16, 2017
• Primary Completion: August 9, 2018
• Study Completion: August 9, 2018
• Last Updated: September 28, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (7); HU (6); PL (7)