Mechanisms of Sleep Disruption Hyperalgesia (ESP2)
1 de agosto de 2019 atualizado por: Johns Hopkins University
Twenty percent of Americans suffer from chronic pain.
Sleep disturbance is similarly prevalent and among the most common and disabling neurobehavioral problems associated with chronic pain.
This research is designed to evaluate the effects of disrupted sleep patterns on mood, inflammation, the perception of pain, and pain relief.
This study will help researchers understand the relationship between sleep and pain, and how sleep disturbance might influence chronic pain conditions.
Visão geral do estudo
Status
Concluído
Condições
Descrição detalhada
This research is being conducted in order to evaluate the effects of disrupted sleep patterns on mood, inflammation, the perception of pain, and pain relief. This study will help researchers understand the relationship between sleep and pain, and how sleep disturbance might influence chronic pain conditions. Healthy participants will undergo baseline sleep and sleep disruption conditions. Following undisturbed sleep and sleep disruption conditions, sensitivity to pain and analgesic response (via morphine or placebo administration) will be assessed using a heat-capsaicin pain model.
This study will be conducted in 2 major parts-3 screening visits (2 outpatient and 1 inpatient) and 2 experimental inpatient visits. Part 1 of the study will involve a 1-week screening period. This will involve two separate screening visits lasting about 2 hours each. At Screening Visit 1, participants will complete questionnaires, an interview, and undergo toxicology screening. At Screening Visit 2, participants will complete questionnaires, undergo a physical exam, and be familiarized with pain testing procedures. At Screening Visit 3, participants will undergo an inpatient sleep study.
Part 2 will involve two different inpatient admissions. The two admissions will be separated by at least two weeks. During each of the admissions, participants' sleep will be studied at night. The first admission will begin immediately following the overnight sleep study in Screening Visit 3. One of the admissions will be for one night and the other admission will be for three nights. For the one night admission, participants will sleep undisturbed for an 8-hour period. For the three night admission, participants will undergo sleep disruption for two nights in a row. On the third night, participants will be allowed to sleep undisturbed for 8 hours for recovery.
During both inpatient admissions, pain testing procedures will be completed that will last approximately 5 hours during the day. During testing, small amounts of blood will be drawn for analysis. Participants will be randomly assigned to two groups. Group A will be given a standard dose of morphine during pain testing. Group B will be given a placebo during pain testing.
Tipo de estudo
Intervencional
Inscrição (Real)
100
Estágio
- Não aplicável
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Maryland
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Baltimore, Maryland, Estados Unidos, 21224
- Johns Hopkins University Bayview Medical Center
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos a 48 anos (Adulto)
Aceita Voluntários Saudáveis
Sim
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion Criteria:
- Healthy
- Age 18-48
- Meets Research Diagnostic Criteria for Normal Sleepers
- Stable sleep phase within 21:00 and 08:00
- Total sleep time between 6.5 and 8.5 hours per night
- Sleep efficiency ≥85%
- Epworth Sleepiness Scale Score <10
- Non-smoker/non-nicotine users
- Low Caffeine Users (≤2 cups per day)
Exclusion Criteria:
- Body Mass Index ≥35
- Lifetime history of chronic pain (>6 months)
- Acute pain
- Significant medical or psychiatric morbidity within 6 months
- Lifetime history of bipolar disorder, psychotic disorder, serious recurrent major depression, serious post-traumatic stress disorder, or seizure disorder
- Respiratory, hepatic, renal, or cardiac conditions that would contraindicate opioid use
- Lifetime history of alcohol or substance abuse or dependence
- Lifetime history of opioid use >36 doses or >7 days of consecutive use
- Prior adverse reaction to general anesthetics, opioids, or capsaicin
- Clinically significant abnormal complete blood count or comprehensive metabolic profile
- Positive toxicology screen for opioids or recreational drugs
- Pregnant or lactating women
- Significant pre-admission psychological distress (T-scores >64 on the Brief Symptom Inventory Global Scales)
- Significant lifetime history of serious head injury that is determined to influence pain processing or sleep systems
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Ciência básica
- Alocação: Randomizado
- Modelo Intervencional: Atribuição cruzada
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Morphine US then Morphine FA
Participants randomized to receive Morphine and the Uninterrupted Sleep (US) condition first.
After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of uninterrupted sleep (US).
With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of forced awakenings (FA).
They will receive the Morphine injection (0.08mg/kg) via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the US and FA sleep conditions are completed.
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0.08mg/kg will be administered to participants randomly assigned to receive the drug via IV bolus during each quantitative sensory testing session (after one night of uninterrupted sleep and after 2 nights of forced awakenings).
Participants will be awakened each hour during an 8 hour sleep opportunity period.
One of the awakenings is for 60 minutes and randomly determined.
The other 7 awakenings are for 20 minutes each, and are randomly scheduled to occur in either the first second or third tertile of each hour.
The maximum total sleep time a participant will receive is 280 minutes.
Participants will receive an 8 hour period of undisturbed sleep
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Comparador de Placebo: Placebo US then Placebo FA
Participants randomized to receive the saline placebo and the Uninterrupted Sleep (US) condition first.
After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of uninterrupted sleep (US).
With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of forced awakenings (FA).
They will receive the injection via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the US and FA sleep conditions are completed.
|
Participants will be awakened each hour during an 8 hour sleep opportunity period.
One of the awakenings is for 60 minutes and randomly determined.
The other 7 awakenings are for 20 minutes each, and are randomly scheduled to occur in either the first second or third tertile of each hour.
The maximum total sleep time a participant will receive is 280 minutes.
Participants will receive an 8 hour period of undisturbed sleep
Saline Placebo will administered to participants randomly assigned to receive the placebo via IV bolus during each quantitative sensory testing session (after one night of uninterrupted sleep and after 2 nights of forced awakenings).
|
|
Experimental: Morphine FA then Morphine US
Participants randomized to receive Morphine and the Forced Awakenings (FA) condition first.
After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of forced awakenings (FA).
With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of uninterrupted sleep (US).
They will receive the Morphine injection (0.08mg/kg) via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the FA and US sleep conditions are completed.
|
0.08mg/kg will be administered to participants randomly assigned to receive the drug via IV bolus during each quantitative sensory testing session (after one night of uninterrupted sleep and after 2 nights of forced awakenings).
Participants will be awakened each hour during an 8 hour sleep opportunity period.
One of the awakenings is for 60 minutes and randomly determined.
The other 7 awakenings are for 20 minutes each, and are randomly scheduled to occur in either the first second or third tertile of each hour.
The maximum total sleep time a participant will receive is 280 minutes.
Participants will receive an 8 hour period of undisturbed sleep
|
|
Comparador de Placebo: Placebo FA then Placebo US
Participants randomized to receive the saline placebo and the Forced Awakenings (FA) condition first.
After a polysomnography (PSG) screening night, participants were randomized to receive two consecutive nights of forced awakenings (FA).
With a minimum of a two week washout period, participants then completed the opposing sleep condition of two nights of uninterrupted sleep (US).
They will receive the injection via IV bolus over 30 seconds during each experimental quantitative sensory testing session that occurs after the FA and US sleep conditions are completed.
|
Participants will be awakened each hour during an 8 hour sleep opportunity period.
One of the awakenings is for 60 minutes and randomly determined.
The other 7 awakenings are for 20 minutes each, and are randomly scheduled to occur in either the first second or third tertile of each hour.
The maximum total sleep time a participant will receive is 280 minutes.
Participants will receive an 8 hour period of undisturbed sleep
Saline Placebo will administered to participants randomly assigned to receive the placebo via IV bolus during each quantitative sensory testing session (after one night of uninterrupted sleep and after 2 nights of forced awakenings).
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Spinal Sensitization as Assessed by Area of Secondary Hyperalgesia (2HA) After Two Nights of Uninterrupted Sleep and Two Nights of 8 Forced Awakenings
Prazo: Next day during quantitative sensory testing after 2 nights of forced awakenings or uninterrupted sleep
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The area of secondary hyperalgesia (2HA) to mechanical stimulation was quantified by stimulating along eight linear paths near the capsaicin treated site using a 15 gram nonpainful von Frey filament.
Stimulation occurred until the participant reported a change in sensation from which a border was marked on the skin.
The degree of 2HA was assessed by measuring the total surface area (mm^2) of the marked borders.
Data were collapsed by group to analyze the effects of FA vs US, irrespective of randomization group.
Our Primary Secondary Hyperalgesia outcome was measured prior to injection of either morphine or placebo.
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Next day during quantitative sensory testing after 2 nights of forced awakenings or uninterrupted sleep
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Opioid Analgesia as Assessed by Analgesia Index (Seconds)
Prazo: Next day after 2 nights of forced awakenings or uninterrupted sleep
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After 2 nights of forced awakenings and after two nights of uninterrupted sleep, opioid analgesia will be assessed by an analgesia index.
The analgesia index is calculated using withdrawal latency during cold pressor testing (lasting maximum of 300 seconds).
Cold Pressor Testing is done before and after morphine or placebo injection.
The difference in withdrawal time before and after morphine or placebo injection is the analgesia index with a minimum score of -300 seconds and maximum score of 300 seconds.
These data were log transformed.
Mean analgesia index was then calculated for each group.
Higher means represent greater analgesia.
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Next day after 2 nights of forced awakenings or uninterrupted sleep
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Mean Change in Percentage of Peripheral Blood Mononuclear Cells Expressing Interleukin-6 After LPS Stimulation
Prazo: Next day after 2 nights of forced awakenings or uninterrupted sleep, every 60 minutes up to 7 hours
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After 2 nights of forced awakenings, and two nights of uninterrupted sleep, blood is drawn (approximately every 60 minutes) during quantitative sensory testing; 4 hours pre-morphine/placebo administration and 2 hours post-morphine/placebo administration to examine markers of inflammation.
Two blood samples for each participant are analyzed at 7 separate time points.
The marker of inflammation assessed is the number of peripheral blood mononuclear cells expressing Interleukin-6 (IL-6), and the outcome measure represents the mean change in IL-6 levels pre and post stimulation with lipopolysaccharide (LPS).
Cellular IL-6 expression was was quantified via flow cytometry.
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Next day after 2 nights of forced awakenings or uninterrupted sleep, every 60 minutes up to 7 hours
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Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Total Sleep Time
Prazo: Next day during quantitative sensory testing after 2 nights of forced awakenings or uninterrupted sleep.
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The degree of sleep deprivation will be assessed by total sleep time (TST) in minutes during the uninterrupted sleep condition compared to the forced awakenings conditions.
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Next day during quantitative sensory testing after 2 nights of forced awakenings or uninterrupted sleep.
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Michael Smith, Ph.D, Johns Hopkins University
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo (Real)
1 de maio de 2013
Conclusão Primária (Real)
1 de janeiro de 2018
Conclusão do estudo (Real)
12 de março de 2019
Datas de inscrição no estudo
Enviado pela primeira vez
15 de fevereiro de 2013
Enviado pela primeira vez que atendeu aos critérios de CQ
15 de fevereiro de 2013
Primeira postagem (Estimativa)
20 de fevereiro de 2013
Atualizações de registro de estudo
Última Atualização Postada (Real)
2 de agosto de 2019
Última atualização enviada que atendeu aos critérios de controle de qualidade
1 de agosto de 2019
Última verificação
1 de agosto de 2019
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Transtornos Mentais, Desordem Mental
- Doenças do Sistema Nervoso
- Dissônias
- Distúrbios do Sono Vigília
- Manifestações Neurológicas
- Distúrbios da Sensação
- Distúrbios somatossensoriais
- Privação de sono
- Hiperalgesia
- Efeitos Fisiológicos das Drogas
- Depressores do Sistema Nervoso Central
- Agentes do Sistema Nervoso Periférico
- Analgésicos
- Agentes do Sistema Sensorial
- Analgésicos, Opioides
- Narcóticos
- Morfina
Outros números de identificação do estudo
- NA_00071465
- 1R01DA032922-01 (Concessão/Contrato do NIH dos EUA)
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .