GAMBIT Task for PTSD

(GAMBIT Trial)

Overseen By Jonathan DePierro

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Opioids, Benzodiazepines

Disqualifiers: Schizophrenia, Bipolar, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a digital training tool called GAMBIT might assist people with PTSD (post-traumatic stress disorder) by examining changes in brain function, behavior, and symptoms. Participants will complete tasks using GAMBIT to determine its effectiveness in improving their condition. The trial includes two groups: one for individuals with PTSD and another for healthy individuals to compare results. Ideal candidates for the PTSD group have experienced a traumatic event and currently exhibit PTSD symptoms, while participants in the healthy group have no psychiatric history. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could lead to new PTSD treatments.

Will I have to stop taking my current medications?

The trial requires that you stop taking opioid medications and certain benzodiazepines at least two weeks before starting. If you are using other medications, the protocol does not specify, so it's best to discuss with the study team.

What prior data suggests that the GAMBIT Task is safe for participants with PTSD?

Research has shown that the GAMBIT task is being tested as a new method to help people with PTSD. Since this is an early study, limited information exists about its safety. However, as a digital exercise rather than a medication, the GAMBIT task is less likely to cause physical side effects compared to traditional treatments. The study aims to determine if the task can improve brain flexibility and behavior in people with PTSD. While no benefits can be promised, the task is expected to pose a low safety risk. Participants will engage in tasks and assessments during the study. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the GAMBIT Task for PTSD because it offers a novel approach to addressing symptoms that traditional treatments, like cognitive behavioral therapy and medication, might not fully alleviate. Unlike these standard options, which often focus on managing symptoms or altering thought patterns, the GAMBIT Task aims to actively engage and potentially rewire specific brain networks involved in PTSD. This approach could lead to more targeted and effective relief of PTSD symptoms, offering hope for those who haven't found success with existing therapies.

What evidence suggests that the GAMBIT Task is effective for PTSD?

Research shows that the GAMBIT Task aims to help people with PTSD by improving their ability to control behavior. This digital training focuses on making brain connections more flexible, potentially reducing PTSD symptoms. In this trial, participants in both the PTSD Group and the Healthy Control Group will receive the GAMBIT intervention. Although this is the first study examining its effects on PTSD, early results suggest it aids in behavior control. By enhancing this control, the task might better manage PTSD symptoms. While data collection on its effectiveness for PTSD continues, this approach appears promising because it targets changes in the brain and behavior. ^{1 2 4 6 7}

Who Is on the Research Team?

Jonathan DePierro, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-55 who either have PTSD or are healthy controls without any psychiatric disorders. Participants must understand English well enough to consent and complete study requirements. Those with moderate PTSD symptoms for at least 3 months can join, but not if they're on certain medications, have cognitive impairments, substance use disorders within the last year, or are currently in specific psychotherapies for PTSD.

Inclusion Criteria

Must meet criteria for one of the following study groups:

I have never been diagnosed with a psychiatric disorder.

Participants must be able to provide informed consent

Exclusion Criteria

Current cognitive impairment, as defined by a score <23 on the Montreal Cognitive Assessment (MoCA)

I am currently in therapy for PTSD using recognized methods.

Substance use disorder within the past 1 year

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pilot Phase

Healthy Control participants complete the GAMBIT intervention and study tasks

up to 52 days

5 visits (in-person)

Treatment

Participants receive the GAMBIT intervention and complete study tasks and assessments

6 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GAMBIT Task

Trial Overview The GAMBIT Task pilot study is testing a digital training task to see how it affects brain flexibility, behavior, and symptoms in people with PTSD compared to healthy individuals without psychiatric conditions.

How Is the Trial Designed?

Group I: PTSD Group Experimental Treatment 1 Intervention

The PTSD Group will receive the GAMBIT intervention and complete all study tasks and assessments at every study visit (Visits 0-4). N=20 participants will be recruited for this arm.

Group II: Healthy Control Group Experimental Treatment 1 Intervention

The Healthy Control Group will receive the GAMBIT intervention and complete all study tasks and assessments at every study visit (Visits 0-4). N=20 participants will be recruited for this arm. Additionally, N=10 Healthy Control participants will be recruited for the Pilot Phase of the study.

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Published Research Related to This Trial

In a study of 143 participants, those with severe PTSD symptoms (PTSS) showed better visual discrimination performance than those with few or no symptoms, particularly in challenging tasks with low spatial separation.

The PTSS group made quicker decisions without slower reaction times, suggesting a unique cognitive processing style that may influence how PTSD symptoms are expressed and maintained, highlighting the need for further research on visual discrimination and generalization in PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-traumatic stress symptoms are associated with better performance on a delayed match-to-position task. Caulfield, MD., Myers, CE.[2020]

In a study of 166 army combat personnel, high levels of cumulative interpersonal trauma were linked to changes in brain activity related to inhibitory control, which may contribute to increased PTSD symptoms after deployment.

The timing of trauma exposure also played a significant role, with adolescent-onset trauma affecting brain responses differently than childhood-onset trauma, suggesting that tailored strategies are needed to improve inhibitory control in military personnel based on their trauma history.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cumulative trauma load and timing of trauma prior to military deployment differentially influences inhibitory control processing across deployment. Miller, LN., Forbes, D., McFarlane, AC., et al.[2023]

In a study of patients with chronic PTSD undergoing prolonged exposure therapy, higher adherence to imaginal homework assignments significantly predicted greater symptom improvement and increased chances of achieving remission and good end-state functioning.

Patients' perceptions of the helpfulness of both imaginal and in vivo homework assignments were also linked to better treatment outcomes, suggesting that tailoring homework to enhance perceived relevance could further improve clinical gains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Homework "Dose," Type, and Helpfulness as Predictors of Clinical Outcomes in Prolonged Exposure for PTSD. Cooper, AA., Kline, AC., Graham, B., et al.[2023]

The study outlines a design for a web-based cognitive remediation training aimed at enhancing neurocognitive functions that may help prevent the development of PTSD in trauma survivors.

By focusing on early intervention shortly after trauma exposure, the study aims to address the challenges of administering targeted training to improve emotional reactivity and regulation, potentially reducing PTSD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating web-based cognitive-affective remediation in recent trauma survivors: study rationale and protocol. Fine, NB., Achituv, M., Etkin, A., et al.[2020]

In a study of 482 U.S. veterans with PTSD, over half received no psychotherapy, and only 8% met the recommended standard of eight sessions within 14 weeks, indicating a significant gap in treatment access.

Despite some participants receiving SSRIs or SNRIs and psychotherapy, the amount of treatment did not correlate with greater symptom improvement, suggesting that treatment effectiveness should be evaluated based on patient outcomes rather than just the quantity of care provided.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations of psychotherapy dose and SSRI or SNRI refills with mental health outcomes among veterans with PTSD. Shin, HJ., Greenbaum, MA., Jain, S., et al.[2022]

Combat-deployed veterans with PTSD show heightened attention to unexpected stimuli during learning, which may contribute to their disproportionate reactions, as indicated by changes in neural activity related to attention allocation.

The study suggests that targeting the mechanisms of attention-based learning could be a potential treatment strategy for PTSD, as increased associability values were linked to both PTSD severity and behavioral choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associability-modulated loss learning is increased in posttraumatic stress disorder. Brown, VM., Zhu, L., Wang, JM., et al.[2020]

Former World War II prisoners of war with PTSD showed average IQ levels and significant cognitive dysfunction, particularly in frontal lobe functions and psychomotor speed, compared to those without PTSD.

Higher IQ may serve as a protective factor against developing long-term PTSD after trauma, while cognitive impairments are more pronounced in PTSD patients with additional psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive dysfunctions associated with PTSD: evidence from World War II prisoners of war. Hart, J., Kimbrell, T., Fauver, P., et al.[2008]

Patients with PTSD showed slower learning in a decision-making task compared to controls, indicating potential deficits in decision-making processes associated with the disorder.

Neuroimaging revealed that PTSD patients had reduced activation in key reward-related brain areas (nucleus accumbens and mesial prefrontal cortex) when processing gains, suggesting that positive outcomes may be less motivating for them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Altered reward processing in the nucleus accumbens and mesial prefrontal cortex of patients with posttraumatic stress disorder. Sailer, U., Robinson, S., Fischmeister, FP., et al.[2014]

Combat Veterans with PTSD demonstrated an intact error-related negativity (ERN) during performance monitoring tasks, indicating that their ability to recognize errors is preserved despite other cognitive control impairments.

The study suggests that this intact error monitoring could be utilized in therapeutic approaches for PTSD, such as neurofeedback and mindfulness training, to enhance emotional awareness and self-monitoring skills.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intact error monitoring in combat Veterans with post-traumatic stress disorder. Swick, D., Honzel, N., Turken, U.[2018]

This Phase 1b trial involves 24 participants with PTSD, testing the NMDAR antagonist lanicemine for its safety, tolerability, and potential efficacy in reducing behavioral sensitization, which is linked to heightened anxiety and stress responses.

The study uniquely focuses on measuring the drug's engagement with NMDARs and its effects on anxiety-potentiated startle responses, rather than just symptom severity, which may provide a new approach for evaluating treatments in psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Proof-of-Mechanism Study to Test Effects of the NMDA Receptor Antagonist Lanicemine on Behavioral Sensitization in Individuals With Symptoms of PTSD. Lijffijt, M., Green, CE., Balderston, N., et al.[2023]

In a study involving 20 veterans with combat-related PTSD, prolonged exposure (PE) therapy led to significant improvements in inhibitory control, as evidenced by better performance on a stop-signal task (SST) after treatment.

Neuroimaging results showed that changes in brain activation related to prediction errors were linked to reductions in PTSD symptoms, suggesting that PE therapy enhances inhibitory learning and helps modify responses to trauma-related cues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurocomputational Changes in Inhibitory Control Associated With Prolonged Exposure Therapy. Harlé, KM., Spadoni, AD., Norman, SB., et al.[2021]

Participants recently exposed to trauma (TE) showed an overgeneralization of fear responses, indicating that their brains did not differentiate between safety and threat cues, which was not observed in non-trauma-exposed participants (NTE).

Neural activity in the dorsomedial prefrontal cortex (PFC) of TE participants was linked to their threat expectancy and predicted the severity of PTSD symptoms three months after the trauma, suggesting that early brain responses can provide insights into future PTSD development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trauma exposure acutely alters neural function during Pavlovian fear conditioning. Harnett, NG., Ference, EW., Wood, KH., et al.[2020]

Citations

1. withpower.com withpower.com/trial/phase-stress-disorders-post-traumatic-4-2022-1ab82

GAMBIT Task for PTSD · Info for Participants This trial tests a computer-based exercise called GAMBIT to help people with PTSD improve their behavior control. The goal is to see if this can reduce PTSD ...

2. mountsinai.org mountsinai.org/clinical-trials/gambit-task-with-ptsd-healthy-control-participants

GAMBIT Task with PTSD and Healthy Control Participants This study will be the first to examine potential relationships between GAMBIT task completion and brain circuit flexibility, behavior, and symptoms in ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05313334/gambit-task-with-ptsd-and-healthy-control-participants

GAMBIT Task with PTSD and Healthy Control Participants This is a pilot study of a digital training task called GAMBIT. This study will be the first to examine potential relationships between ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05313334

GAMBIT Task with PTSD and Healthy Control Participants This is a single-site pilot study for the GAMBIT intervention, which is a computerized task that addresses behavioral inhibition. The primary objective of ...

5. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/34/NCT05313334/ICF_000.pdf

Gamified Approach to Maximizing Biobehavioral Inhibition ... Plus, the data collected during this study will provide valuable information about the GAMBIT task and its potential effectiveness with PTSD patients. Since ...

6. clinicaltrial.be clinicaltrial.be/en/details/30227?only_active=0&only_eligible=0&only_recruiting=1&per_page=100

GAMBIT Task With PTSD and Healthy Control Participants -... The primary objective of this study is to determine whether the GAMBIT task improves mental health symptoms associated with PTSD over time. The ...

7. go.drugbank.com go.drugbank.com/conditions/DBCOND0038601

Post Traumatic Stress Disorder (PTSD) (DBCOND0038601) GAMBIT Task with PTSD and Healthy Control Participants, No drug interventions ... Clinical Trial to Preliminarily Assess the Safety and Feasibility of ...