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Evaluation of the Initial Prescription of Ketamine and Milnacipran in Depression in Patients With a Progressive Disease

Phase 2
Recruiting
Conditions
Depression
Interventions
Registration Number
NCT02783430
Lead Sponsor
University Hospital, Lille
Brief Summary

KetaPal is a placebo-controlled randomized trial designed to demonstrate the antidepressant action of ketamine in palliative care situations. Half of participants will receive Ketamine and Milnacipran in combination, while the other half will receive a Placebo and Milnacipran in combination.

Detailed Description

Ketamine, a molecule mainly used as an analgesic in palliative care, turns out to be an excellent fast acting antidepressant. By acting as an NMDA receptor antagonist, its mechanism of action is complementary to classical and long acting antidepressants like Selective Serotonin Reuptake Inhibitors (SSRI). In particular, ketamine is able to boost synaptogenesis in only a few hours whereas long-term prescription of SSRI can stimulate neurogenesis.

The purpose of this study is to evaluate a new therapeutic strategy that could integrate ketamine in the same time than SSRI, to control depression symptoms faster and optimize patient's quality of life complementary to treatments of cancer.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
80
Inclusion Criteria
  • Inpatient
  • Supported by a functional palliative care unit
  • Having a severe and progressive disease diagnosed
  • Meet the criteria for major depressive disorder as defined by DSM in its version 5
  • MADRS > 19 ( moderate to severe)
  • No antidepressant treatment or treatment introduced for more than four weeks
  • In ability to receive clear information and give consent
  • Beneficiary of a social security scheme
Exclusion Criteria
  • upper weight or equal to 100 kg
  • ultimate phase (about 24 to 72 hours prior to death)
  • unstable patient on cardiovascular diseases, including uncontrolled hypertension
  • severe renal impairment (renal clearance less than 15 ml / min)
  • psychiatric comorbidity: schizophrenia and schizoaffective disorder
  • neurological comorbidity: recent cerebrovascular accident (Less than one month), Parkinson's disease, dementia
  • treatment with ketamine received in the four weeks preceding the inclusion
  • impaired judgment, cognitive or massive sensory impairment not allowing to receive clear information
  • oral antidepressant treatment introduced less than four weeks ago
  • dosage of oral antidepressant treatment upper than the marketing authorization for more than four weeks
  • patient not covered by the social security system
  • refusal to sign the consent
  • minor patient or guardianship
  • pregnant women (implementation of a urine pregnancy test before inclusion for women of childbearing age)
  • lactating women
  • intolerance or allergic reaction to ketamine or milnacipran.
  • contraindications to the association of ketamine or milnacipran with the patient's usual treatment

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Milnacipran + PlaceboPlaceboPlacebo single intravenous perfusion during 40 minutes. Milnacipran dosage depending of glomerular filtration rate of patient, during 16 days (doses of 25 or 50 mg or 100mg per day)
Milnacipran + KetamineMilnacipranKetamine 0,5mg/kg single intravenous perfusion during 40 minutes. Milnacipran dosage depending of glomerular filtration rate of patient, during 16 days (doses of 25 or 50 mg or 100mg per day)
Milnacipran + KetamineKetamineKetamine 0,5mg/kg single intravenous perfusion during 40 minutes. Milnacipran dosage depending of glomerular filtration rate of patient, during 16 days (doses of 25 or 50 mg or 100mg per day)
Milnacipran + PlaceboMilnacipranPlacebo single intravenous perfusion during 40 minutes. Milnacipran dosage depending of glomerular filtration rate of patient, during 16 days (doses of 25 or 50 mg or 100mg per day)
Primary Outcome Measures
NameTimeMethod
MADRS ScoreAt day 1, At day 2

Measure of the change of Depression Intensity

Secondary Outcome Measures
NameTimeMethod
Hospital Anxiety and Depression scale (HAD)at day 0, at day 1, at day 2, at day 4, at day 8, at day 15

The items of the scale limit confounding factors related to physical comorbidity . The answers are simple and quick . It is a wide choice and recommended for depression studies in palliative care.

MADRS Scoreat day 0, at day 4, at day 8, at day 15

The MADRS scale quantifies the intensity of depressive symptoms, determine the number of responders (reduction in the initial score greater than or equal to 50%) and the number of patients in remission (score less than 7).

Global Assessment Scale Operation (EGF)at day 0, at day 15

Global Assessment of Functioning is a numerical scale ( from 0 to 100) used to evaluate the psychological, social and work of an individual .

Edmonton Symptom Assessment System ( ESAS )at day 0, at day 1, at day 2, at day 4, at day 8, at day 15

Symptom Assessment Scale

Clinical Global Impression (CGI) Scoreat day 0, at day 1, at day 2, at day 4, at day 8, at day 15

These hetero fast and well validated assessments help to complete the assessment by the clinician on the severity of the patient's situation and overall improvement

EUROHIS-QOL 8at day 0, at day 15

Measure of the improvement of quality of life after 15 days of treatment. EUROHIS-QOL 8-item index, a shortened version of the World Health Organization Quality of Life Instrument-Abbreviated Version (WHOQOL-BREF).

Number of request of early death (suicidal intentions or euthanasia or physician-assisted suicide)at day 0, at day 1, at day 2, at day 4, at day 8, at day 15

measure request of suicidal intentions made by the patient on explicit request of the clinician.

Trial Locations

Locations (9)

Chu Amiens Picardie

🇫🇷

Amiens, France

Ch Calais

🇫🇷

Calais, France

Maison Medicale Jean Xxiii - Lille

🇫🇷

Lille, France

Ch Tourcoing

🇫🇷

Tourcoing, France

Ch Ghpso Senlis

🇫🇷

Senlis, France

Groupt Hopitaux Instit Catho de Lille - Lomme

🇫🇷

Lomme, France

Centre Hospitalier de Valenciennes

🇫🇷

Valenciennes, France

University Hospital,

🇫🇷

Lille, France

C.H de Roubaix

🇫🇷

Roubaix, France

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