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Ketamine in Adolescents With Treatment-Resistant Depression

24 gennaio 2020 aggiornato da: University of Minnesota

Open-Label Intravenous Subanesthetic Ketamine for Adolescents With Treatment-Resistant Depression

This study will test the use of ketamine for treatment of depression in adolescents that have not responded to other treatments. We will also examine neurobiological mechanisms of treatment.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

Depression frequently emerges during adolescence and is associated with severe outcomes. Current interventions do not lead to remission for many adolescents. Treatment-resistant depression (TRD) in adolescence is an ominous prognostic indicator for a lifetime of suffering and increased risk for suicide. Efforts should be directed toward novel interventions that could alter this perilous course. Theoretically, restoration of healthy development during this critical window would substantially improve outcomes over the lifespan.

Ketamine is a noncompetitive, high-affinity antagonist of the N-methyl-D-aspartate type glutamate receptor that has long been used for induction and maintenance of anesthesia in children and adults, and recently has been investigated for its rapid antidepressant effects. Randomized, double-blind, saline-controlled trials in adults with TRD have demonstrated that a single, subanesthetic infusion of intravenous (IV) ketamine at 0.5 mg/kg over 40 minutes can produce a rapid (within 2 hours) antidepressant response (Ibrahim et al., 2011; Zarate et al., 2006). Recent evidence suggests that serial doses of ketamine may be even more effective and may lead to more prolonged remission (aan het Rot et al., 2010; Murrough et al., 2012). Our current research at using serial dosing of IV ketamine among adult veterans with TRD over a 2-week period has shown promising results, with a response rate of 92% among the 12 participants to date.

No results from any studies examining effectiveness of either single-dose or serial-dose ketamine have yet been published in adolescents with TRD. Because of the ongoing neurodevelopment in adolescence, which is thought to confer enhanced neuroplasticity, it is possible that adolescents with TRD could show greater responses and more sustained remission than adults with TRD. The biological mechanisms of depression impacted by ketamine are only now being uncovered in adults (Zarate et al., 2013). Characterization of the neural mechanisms underlying ketamine response or non-response in adolescents with TRD will represent a significant advance. The specific aims of this preliminary study are as follows:

Aim #1: To determine the efficacy of repeated-dose subanesthetic IV ketamine among adolescent patients with TRD.

Hypothesis: Based on previous results in adults with TRD, we predict that response rates will improve over the course of six treatments of ketamine.

Aim #2: To explore durability of antidepressant response to repeated dose of IV ketamine in a 4-week observational period.

Hypothesis: Based on the inherent neuroplasticity in adolescence due to ongoing neurodevelopment, adolescents may show a more durable clinical response than has been seen in adults.

Aim #3: To study the neurobiological mechanisms of response to ketamine. We will examine relevant biological systems using several different brain imaging indices and measures of intracellular functioning from peripheral blood.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

14

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Stati Uniti
    • Minnesota
      • Minneapolis, Minnesota, Stati Uniti, 55454
        • University of Minnesota

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 12 anni a 18 anni (Bambino, Adulto)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • Male and female adolescents aged 12 to 18 years.
  • Presence of recurrent major depression without psychotic features confirmed by the Kiddie-Schedule for Affective Disorders and Schizophrenia - Parent and Lifetime Version (Kaufman et al., 1997).
  • Current depression severity measured by the Children's Depression Rating Scale (CDRS) (Poznanski, 1985) raw score greater than or equal to 36 at screening and the day ketamine is due to be received for the first time.
  • Current depressive episode resistant to treatment, defined as failure to achieve remission (elimination of symptoms and restoration of pre-morbid psychosocial functioning) from at least 2 antidepressant trials of different pharmacological classes. Systematic evaluation of previous antidepressant trials will be assessed by using the Antidepressant Treatment History Form (Sackeim, 2001).
  • If present, current antidepressant medication treatment must be dose stable for at least 2 months prior to beginning the study. (Patients will continue with current antidepressant treatment throughout the study. Based on our experience in current research at the VA Medical Center using serial ketamine for adult TRD, patients have shown positive results while continuing their current antidepressant treatment.)

Exclusion Criteria:

  • Inability to speak English
  • Inability or unwillingness to provide written informed consent
  • A history of Mental Retardation or any Pervasive Developmental Disorder
  • Current or lifetime diagnosis of schizophrenia, schizoaffective disorder, or psychosis Not Otherwise Specified.
  • Family history with a first degree relative with schizophrenia, schizoaffective disorder, or psychosis Not Otherwise Specified.
  • Diagnosis of seizures or other neurological disorders.
  • Comorbid diagnosis of substance abuse or dependence, current or past.
  • Clinically unstable medical illness.
  • Current use of the following medications: any barbiturates, any narcotics, any non-benzodiazepine hypnotics at doses higher than zolpidem 10 mg qhs or equivalent for insomnia.
  • For women: pregnancy (confirmed by baseline lab test).
  • The presence of any MRI contra-indications such as MRI-incompatible metals in the body or claustrophobia.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: ketamine
Intravenous ketamine 0.5 mg/kg over 40 minutes will be given 6 times over 2 weeks.
Droga: Ketamine
IV infusions of 0.5mg/kg of Ketamine hydrochloride over a 40-minute infusion period. Participants will receive a total of 6 doses over a 2-week period.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Number of Responders Measured by Clinical Global Impression (CGI)
Lasso di tempo: 2 weeks
Responders will be defined as those with CGI ratings (given by the study clinician) of 1 or 2 (much or very much improved). Patients that are given a scores of 3-7 (minimally improved to very much worse) will be considered non-responders.
2 weeks

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Children's Depression Rating Scale-Revised
Lasso di tempo: 2 weeks
The CDRS-R measure is given in interview form to child and parent separately. A consensus is then created with best-estimate for 17 items (each with a range of 1-5 or 1-7) using both sources of information. The total score is the sum of 17 item scores, ranging from 17-113 with higher scores indicating greater depression symptoms.
2 weeks
Montgomery-Åsberg Depression Rating Scale (MADRS)
Lasso di tempo: 2 weeks
MADRS is a 10-item clinician-administered inventory measuring depression symptoms. Items are scored on a scare from 0 (none) to 6 (constant). Total scores are a sum of the 10 item scores, ranging from 0 to 60, with higher scores indicating greater symptom severity.
2 weeks
Beck Depression Inventory-II (BDI-II)
Lasso di tempo: 2 weeks
BDI-II is a 21-item self-report multiple-choice inventory that assesses the severity of depressive symptoms over the prior week. Items are rated on a 4-point scale ranging from 0 to 3. Total scores are a sum of the 21 item scores ranging from 0 to 63. Higher scores indicate more severe depression symptoms.
2 weeks
Change in Clinician Administered Dissociative States Scale (CADSS)
Lasso di tempo: baseline, 2 weeks
CADSS is a 27-item instrument measuring symptoms of dissociative stress, with 19 items completed by the patient and 8 items completed by the clinician. Items are rated on a scale of 0 (not at all) to 4 (extreme). Total scores are a sum of the 27 item scores and range from 0 to 108, with higher scores indicating greater symptom severity.
baseline, 2 weeks
Maximum Change in Systolic Blood Pressure
Lasso di tempo: 2 hours and 40 minutes
Vital signs were measured every 15 minutes, starting from the beginning of the infusion and ending 2 hours after the infusion ended (2 hours, 40 minutes total). Maximum increase of blood pressure compared to baseline was calculated.
2 hours and 40 minutes
Maximum Change in Diastolic Blood Pressure
Lasso di tempo: baseline, 45 minutes post infusion
baseline, 45 minutes post infusion
Maximum Change in Heart Rate
Lasso di tempo: 4 hours
4 hours
Maximum Decrease in Pulse Oximetry
Lasso di tempo: 4 hours
4 hours

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

University of Minnesota

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 settembre 2014

Completamento primario (Effettivo)

1 marzo 2018

Completamento dello studio (Effettivo)

1 marzo 2018

Date di iscrizione allo studio

Primo inviato

27 febbraio 2014

Primo inviato che soddisfa i criteri di controllo qualità

3 marzo 2014

Primo Inserito (Stima)

5 marzo 2014

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

27 gennaio 2020

Ultimo aggiornamento inviato che soddisfa i criteri QC

24 gennaio 2020

Ultimo verificato

1 gennaio 2020

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 22225

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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