An Investigation of the Effect of MMP-9 Inhibition With Minocycline on the Reconsolidation of Intrusive Trauma- or Cocaine-related Memories
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 138
- 试验地点
- 1
- 主要终点
- Changes in intrusive memories frequency and features
研究概览
简要总结
An investigation of the effect of matrix-metalloproteinase-(MMP)-9 inhibition with minocycline on the reconsolidation of trauma- or cocaine-related memories
详细描述
Intrusive memories are involuntary recollections of past emotional events that can become pathological and persist over time, particularly in post-traumatic stress disorder (PTSD) and cocaine use disorders (CUD). Both PTSD and CUD are characterised by a hypersensitivity and -reactivity to cue-elicited memory reactivation and exhibit common neurological alterations, suggesting shared underlying mechanisms. As intrusive memories significantly contribute to maintaining the cycle of relapse in both disorders, it is important to find a way to attenuate them successfully. Research on memory reconsolidation has led to the development of different (pharmacological) approaches to disrupt the process, which have, however, yielded mixed and unspecific effects so far.
The present project aims to investigate the effect of MMP-9 inhibition with minocycline on the reconsolidation of intrusive memories in individuals with CUD or PTSD. Participants will be randomly assigned to a minocycline or placebo group. The study comprises a total of 5 visits during 3 weeks and one follow-up online survey (3 months after the intervention). Participants will receive the study medication before two imagery script-guided memory activation sessions. An ecological momentary assessment (EMA) approach will be employed to track intrusive memories, and glutamate concentration and neural activation will be measured with magnetic resonance spectroscopy (MRS) and functional magnetic resonance (fMRI), respectively, before and after the two imagery sessions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
盲法说明
double-blinded
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •General Inclusion Criteria:
- •Ability to read, understand and provide written informed consent
- •Age between 18 and 60 years
- •To be sufficiently fluent in German
- •Inclusion Criteria for the PTSD group:
- •- Current diagnosis of full PTSD according to the 5th version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), of subthreshold PTSD, as in meeting two to three of the DSM-5 criteria B-E, or of complex PTSD
- •Inclusion Criteria for the CUD group:
- •Current diagnosis of mild, moderate, or severe CUD according to DSM-5
- •Regular cocaine use in the last 12 months and at least one consumption event in the last 6 months
- •Inclusion Criteria for the Clinical Controls (PTSD+CUD group):
- •Current diagnosis of full PTSD according to the 5th version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), of subthreshold PTSD, as in meeting two to three of the DSM-5 criteria B-E, or of complex PTSD
- •Current diagnosis of mild, moderate, or severe CUD according to DSM-5
- •Regular cocaine use in the last 12 months and at least one consumption event in the last 6 months
排除标准
- •for the HC, PTSD, CUD, and PTSD+CUD groups:
- •Women who are pregnant or breast feeding or intending to become pregnant during the course of the study or within 3 months after
- •Other clinically significant concomitant disease states, e.g., renal failure (i.e., estimated glomerular filtration rate (eGFR; CKD-EPI) lower than 60 ml/min/1.73 m2), hepatic dysfunction (i.e., alanine transaminase (ALT) higher than 90 U/I for women or 110 U/I for men, aspartate aminotransferase (AST) higher than 74 U/I, and/or gamma-glutamyl transferase (γGT) higher than 70 U/I for women or 120 U/I for men), cardiovascular disease, etc.
- •Presence or history of severe neurological disorders, head injuries or systemic/rheumatic disease
- •Diagnosis of schizophrenia, bipolar disorder, or autism spectrum disorder according to DSM-5
- •Pacemaker, neurostimulator or any other head or heart implants as well as MRI-incompatible metal parts or possibility of metal fragments in the body (MR safety)
- •Claustrophobia (MR safety)
- •Dependence on a hearing aid (MR safety)
- •Inability to follow the procedures of the study, e.g., due to language problems
- •Participation in another study with investigational drugs within the 30 days preceding and during the present study
- •More than three suicide attempts in the past, a suicide attempt within the last 12 months and/or acute suicidality
- •Exclusion Criteria for Healthy Controls:
- •Any current psychiatric diagnosis according to DSM-5 except for mild or moderate substance use disorder (SUD) for nicotine, and mild SUD for alcohol and cannabis
- •Diagnosis of CUD according to DSM-5 (lifetime)
- •Diagnosis of PTSD according to DSM-5 (lifetime)
- •Exclusion Criteria for both the PTSD and CUD groups:
- •Allergy to minocycline or to any other ingredient in the named drug
- •Current intake of the following medications interacting with minocycline: acitretin, acetylcystein, aluminiumhydroxid, amitryptiline, any antibiotics, antidiabetic drug such as sulfonylurea, atazanavir, atomoxetine, anticoagulant drugs from the coumarin type, barbiturates, bupropion, carbamazepine, ciclosporin A, isotretinoin, methotrexate, phenytoin, and theophylline
- •Exclusion Criteria for only the PTSD group:
- •Diagnosis of CUD according to DSM-5 (lifetime)
- •Current diagnosis of severe SUD for nicotine, moderate SUD for alcohol and cannabis, and mild SUD for all other substances according to DSM-5
- •Exclusion Criteria for only the CUD group:
- •Diagnosis of PTSD according to DSM-5 (lifetime)
- •Current diagnosis of severe SUD for alcohol or cannabis, and mild SUD for all other substances (except for nicotine) according to DSM-5
- •Exclusion Criteria for Clinical Controls (PTSD+CUD group):
- •- Current diagnosis of severe SUD for alcohol or cannabis, and mild SUD for all other substances (except for nicotine) according to DSM-5
研究组 & 干预措施
PTSD intervention group
30 individuals with PTSD will receive imagery with minocycline.
干预措施: Imagery (Behavioral)
PTSD intervention group
30 individuals with PTSD will receive imagery with minocycline.
干预措施: Minocycline (Drug)
PTSD control group
30 individuals with PTSD will receive imagery with placebo.
干预措施: Imagery (Behavioral)
PTSD control group
30 individuals with PTSD will receive imagery with placebo.
干预措施: Placebo (Drug)
CUD intervention group
30 individuals with CUD will receive imagery with minocycline.
干预措施: Imagery (Behavioral)
CUD intervention group
30 individuals with CUD will receive imagery with minocycline.
干预措施: Minocycline (Drug)
CUD control group
30 individuals with CUD will receive imagery with placebo.
干预措施: Imagery (Behavioral)
CUD control group
30 individuals with CUD will receive imagery with placebo.
干预措施: Placebo (Drug)
Healthy control group
30 healthy individuals who will not receive any intervention.
Clinical control group
30 individuals with both PTSD and CUD who will not receive any intervention
Healthy control group for memory narratives
30 healthy individuals who will not receive any intervention, who undergo an online memory assessment only to improve comparability of text-based language features between healthy controls and participants with a PTSD or CUD diagnosis (HCN group)
结局指标
主要结局
Changes in intrusive memories frequency and features
时间窗: Changes from baseline intrusive memories frequency and features after both 9 to 39 days (follow-up 1) and approx. 3.5 months (follow-up 2)
Measured with the Intrusion Questionnaire, containing various items on intrusive memories frequency, arousal and distress as well as triggers, and responses.
Change over time in self-reported intrusive memories frequency, arousal and distress
时间窗: EMA will be conducted for an average of 12 to 42 days (through study participation from baseline to 3 days after follow-up 1).
Captured with a short version of the Intrusion Questionnaire implemented as smartphone-based ecological momentary assessment (EMA), containing items on arousal and distress from self-reported intrusive memories.
次要结局
- Change in MMP-9 protein levels(Change from baseline MMP-9 protein levels after 9 to max. 39 days (follow-up 1).)
- Change in MMP-9 gene expression(Change from baseline MMP-9 gene expression after 9 to max. 39 days (follow-up 1).)
- Change in heart rate variability (HRV) during fMRI memory reactivation(Change from baseline HRV after 9 to max. 39 days (follow-up 1).)
- Change in respiratory rate during fMRI memory reactivation(Change from baseline respiratory rate after 9 to max. 39 days (follow-up 1).)
- Change in subjective rating of distress before and after memory reactivation(Change from baseline subjective distress after 9 to max. 39 days (follow-up 1).)
- Change in subjective rating of craving before and after memory reactivation(Change from baseline craving after 9 to max. 39 days (follow-up 1).)
- Change in neurofilament light chain (NfL) levels(Change from baseline NfL levels after 9 to max. 39 days (follow-up 1).)
- Change in sphingolipid levels(Change from baseline sphingolipid levels after 9 to max. 39 days (follow-up 1).)
- Change in inflammatory biomarker levels(Change from baseline inflammatory levels after 9 to max. 39 days (follow-up 1).)
- Heartrate variability(Will be measured during 9 to max. 39 days, from baseline until follow-up 1.)
- Sleep duration(Will be measured during 9 to max. 39 days, from baseline until follow-up 1.)
- Change in Obsessive Compulsive Cocaine Use Scale (OCCUS)(Change from baseline OCCUS score after both 9 to 39 days (follow-up 1) and approx. 3.5 months (follow-up 2).)
- PTSD Checklist for DSM-5 (PCL-5)(Change from baseline PCL-5 score after both 9 to 39 days (follow-up 1) and approx. 3.5 months (follow-up 2).)
- Beck Depression Inventory-II (BDI-II)(Change from baseline BDI-II score after both 9 to 39 days (follow-up 1) and approx. 3.5 months (follow-up 2).)
- Pittsburgh Sleep Quality Index (PSQI)(Change from baseline PSQI score after both 9 to 39 days (follow-up 1) and approx. 3.5 months (follow-up 2).)
- Global Assessment of Functioning (GAF)(Change from screening GAF score after both 10 to 50 days (follow-up 1) and approx. 4 months (follow-up 2).)
- Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)(Change from screening CAPS-5 score after approx. 4 months (follow-up 2).)
- Changes in the Interview for Psychotropic Drug Consumption (IPDC)(Change from screening IPDC after approx. 4 months (follow-up 2).)
- Voice-recorded language features of memories(Assessed at screening)
- Changes in MRS signal parameters(Change from baseline MRS-measured glutamate concentrations after 9 to max. 39 days (follow-up 1).)
- Changes in fMRI Blood-Oxygenation-Level Dependent (BOLD) contrasts(Changes from baseline fMRI BOLD contrasts after 9 to max. 39 days (follow-up 1).)