Trazodone in Painful Diabetic Neuropathy

Painful Diabetic Neuropathy Clinical Trial

Official title:

Efficacy and Safety of Low Doses of Trazodone in Patients Affected by Painful Diabetic Neuropathy: Randomized, Controlled, Pilot Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03202979
• Other study ID #: 039(B)PO16143
• Secondary ID: 2016-002772-27
• Status: Completed
• Phase: Phase 2
• Start date: May 16, 2017
• Est. completion date: August 9, 2018

Study information

• Verified date: September 2018
• Source: Aziende Chimiche Riunite Angelini Francesco S.p.A
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a randomized, double-blind, placebo controlled, double-dummy, dose finding, parallel group, multicentre, international, prospective, pilot study.

The present study is planned to assess the efficacy and the safety of an 8-week treatment period with low doses of trazodone (30 mg daily or 60 mg total daily, respectively) administered to patients affected by painful diabetic neuropathy.

Gabapentin will be administered together with the investigational drug in open label conditions in order to assure an effective pharmacological treatment to all patients. A slow titration of gabapentin will be applied in this trial in order to control possible side effects when co-administered with trazodone.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 142
• Est. completion date: August 9, 2018
• Est. primary completion date: August 9, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Male and female patient of any ethnic origin between 18 and 75 years of age (limits included).

2. Patient with painful diabetic symmetric polyneuropathy manifesting with distally distributed neuropathic pain.

3. Stable glycaemic control with a value of HbA1c = 10% at Screening Visit.

4. Pain persisting for at least 3 months.

5. Neuropathic pain confirmed by DN4 score = 4 at Screening Visit.

6. BPI-SF 24-hour average pain score (item 5) = 4 at Screening Visit and Baseline Visit.

7. 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.

8. 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.

9. Legally capable to give their consent to participate in the study and available to sign and date the written informed consent.

Exclusion Criteria:

1. Known hypersensitivity to trazodone or gabapentin or their excipients.

2. 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).

3. Concomitant treatment with other medications for pain management.

4. Concomitant treatment with potent CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, indinavir) or drugs known to prolong QT interval.

5. Use of trazodone or gabapentin in the previous 3 months.

6. 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.

7. Active foot ulcer or previous major limb amputation.

8. Myocardial infarction or angioplasty or by-pass graft procedures within the past 6 months.

9. 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.

10. Transient ischemic attack or cerebral vascular accident within the past 6 months.

11. GFR value < 60 ml/min calculated with MDRD formula.

12. Significant liver disease, defined as known active hepatitis or elevated liver enzymes over 3 fold the upper normal limit of laboratory normal ranges.

13. Patient with latent or known hereditary problems of galactose intolerance or the Lapp lactase deficiency or glucose-galactose malabsorption.

14. Positive urine drug screen for CNS active drugs (cocaine, opioids, amphetamines and cannabinoids) a Screening Visit.

15. Positive present history of glaucoma.

16. Hyperthyroidism, even if pharmacologically corrected.

17. Significant mental disorders.

18. History of seizure events other than a single childhood febrile seizure.

19. History of alcohol or psychoactive substance abuse or addiction.

20. Patient suffering from adrenal hypofunction (e.g. Addison's disease).

21. Women during pregnancy or lactation period.

22. Inability to comply with the protocol requirements, instructions or study-related restrictions (e.g. uncooperative attitude, inability to return for study-visits, improbability of completing the clinical study, etc).

23. Subject involved in the conduct of the study (e.g. Investigator or his/her deputy, first grade relatives, pharmacist, assistant or other personnel, etc).

24. Participation to an interventional clinical trial within 3 months prior to Screening Visit.

Related Conditions & MeSH terms

• Diabetic Neuropathies
• Pain
• Painful Diabetic Neuropathy

Intervention

Drug:
• Trazodone 20 mg
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.
• Trazodone 10 mg
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.
• Placebo
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.

Locations

Country	Name	City	State
Czechia	NEUROHK s.r.o.	Chocen
Czechia	Litnea s.r.o. Neurologicka ambulance	Litomerice
Czechia	Neurosanatio s.r.o.	Litomysl
Czechia	MP-neuro s.r.o. Poliklinika Modry pavilon	Ostrava
Czechia	Nemocnice Pardubickeho kraje a.s. Pardubicka nemocnice Neurologická klinika	Pardubice
Czechia	Diabetologicka ambulance Milan Kvapil s.r.o.	Praha 4
Czechia	Vestra Clinics s.r.o.	Rychnov nad Knežnou
Hungary	Budai Irgalmasrendi Korhaz Belgyógyászati Centrum	Budapest
Hungary	Semmelweis Egyetem AOK I. sz. Belgyogyaszati Klinika	Budapest
Hungary	Markhot Ferenc Oktatokorhaz es Rendelointezet Diabetesz Gondozo	Eger
Hungary	Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaz I. sz. Belgyogyaszati Osztaly	Gyula
Hungary	Bacs-Kiskun Megyei Korhaz II. sz. Belgyogyaszati Osztaly	Kecskemet
Hungary	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont I. Sz. Belgyogyaszati Klinika	Szeged
Poland	Pro Familia Altera Sp. z o.o.	Katowice
Poland	Silmedic Sp. z o.o.	Katowice
Poland	NZOZ Neuromed M. i M. Nastaj Sp. P.	Lublin
Poland	RCMed Oddzial Sochaczew	Sochaczew
Poland	Jeka Slawomir Niepubliczny Zaklad Opieki Zdrowotnej "Nasz Lekarz" Praktyka Grupowa Lekarzy Rodzinnych z Przychodnia Specjalistyczna	Torun
Poland	Medycyna Kliniczna	Warszawa
Poland	NBR Polska Tomasz Klodawski	Warszawa

Sponsors (2)

Lead Sponsor	Collaborator
Aziende Chimiche Riunite Angelini Francesco S.p.A	Chiltern International Inc.

Countries where clinical trial is conducted

Czechia,  Hungary,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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 7, 14, 21, 28, 35, 42, 49 and 63 days.	Baseline - Days 7, 14, 21, 28, 35, 42, 49, 63
Secondary	Change of item 3 score in Brief Pain Inventory Short Form (BPI-SF) scale	Change from baseline of item 3 score in BPI-SF numering scale after 7, 14, 21, 28, 35, 42, 49, 56 and 63 days.	Baseline - Days 7, 14, 21, 28, 35, 42, 49, 56 and 63.
Secondary	Change of item 4 score in Brief Pain Inventory Short Form (BPI-SF) scale	Change from baseline of item 4 score in BPI-SF numering scale after 7, 14, 21, 28, 35, 42, 49, 56 and 63 days.	Baseline - Days 7, 14, 21, 28, 35, 42, 49, 56 and 63.
Secondary	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 7, 14, 21, 28, 35, 42, 49, 56 and 63 days.	Baseline - Days 7, 14, 21, 28, 35, 42, 49, 56 and 63.
Secondary	Change of item 6 score in Brief Pain Inventory Short Form (BPI-SF) scale	Change from baseline of item 6 score in BPI-SF numering scale after 7, 14, 21, 28, 35, 42, 49, 56 and 63 days.	Baseline - Days 7, 14, 21, 28, 35, 42, 49, 56 and 63.
Secondary	Change of item 8 score in Brief Pain Inventory Short Form (BPI-SF) scale	Change from baseline of item 8 score in BPI-SF numering scale after 7, 14, 21, 28, 35, 42, 49, 56 and 63 days.	Baseline - Days 7, 14, 21, 28, 35, 42, 49, 56 and 63.
Secondary	Change of item 9 score in Brief Pain Inventory Short Form (BPI-SF) scale	Change from baseline of item 9 score in BPI-SF numering scale after 7, 14, 21, 28, 35, 42, 49, 56 and 63 days.	Baseline - Days 7, 14, 21, 28, 35, 42, 49, 56 and 63.
Secondary	Change in Neuropathic Pain Symptom Inventory (NPSI) scale	Change from baseline of total score in NPSI scale after 7, 14, 21, 28, 35, 42, 49, 56 and 63 days.	Baseline - Days 7, 14, 21, 28, 35, 42, 49, 56 and 63.
Secondary	Change in 36-item Short-Form Health Survey (SF-36)	Change from baseline of SF-36 after 56 days.	Baseline - Day 56
Secondary	Change in Hamilton Anxiety Rating Scale (HAM-A)	Change from baseline of total score in HAM-A scale after 7, 14, 21, 28, 35, 42, 49, 56 and 63 days.	Baseline - Days 7, 14, 21, 28, 35, 42, 49, 56 and 63.
Secondary	Patient Global Impression of Change (PGIC)	Assessment by patient of the overall efficacy and tolerability by PGIC after 7, 14, 21, 28, 35, 42, 49, 56 and 63 days	Days 7, 14, 21, 28, 35, 42, 49, 56 and 63.
Secondary	Change in Leeds Sleep Evaluation Questionnaire (LSEQ)	Change from baseline in LSEQ after 7, 14, 21, 28, 35, 42, 49, 56 and 63 days.	Baseline - Days 7, 14, 21, 28, 35, 42, 49, 56 and 63.
Secondary	Frequency of treatment-related adverse events	Monitoring of the frequency of adverse events, physical examination, vital signs, ECG, laboratory analyses	9 weeks

External Links

•   Sponsor's website