GAMBIT Task for PTSD

(GAMBIT Trial)

Overseen by Jonathan DePierro, PhD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Opioids, Benzodiazepines

Disqualifiers: Schizophrenia, Bipolar, Substance use, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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 symptoms by enhancing their ability to manage reactions and behaviors.

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 data supports the effectiveness of the GAMBIT Task treatment for PTSD?

The research suggests that targeted neurocognitive training, like the GAMBIT Task, may help improve brain functions related to PTSD, potentially reducing symptoms. This is based on evidence that retraining brain systems involved in emotion and decision-making can enhance their efficiency and help prevent PTSD. ^{1 2 3 4 5}

What safety data exists for the GAMBIT Task treatment for PTSD?

The study involving the NMDA receptor antagonist lanicemine, which may be related to the GAMBIT Task, is a Phase 1b trial that examines safety and tolerability in individuals with PTSD. This suggests that the treatment is in early stages of testing for safety in humans. ^{4 6 7 8 9}

How does the GAMBIT Task treatment for PTSD differ from other treatments?

The GAMBIT Task treatment for PTSD is unique because it focuses on improving cognitive processes like visual discrimination and decision-making speed, which are often altered in PTSD. Unlike traditional therapies that primarily address emotional symptoms, this treatment targets cognitive functions that may contribute to PTSD symptoms. ^{2 5 10 11 12}

Research Team

Jonathan DePierro, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• GAMBIT Task (Behavioral Intervention)

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.

Participant Groups

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+

Dr. Brendan Carr

Icahn School of Medicine at Mount Sinai

Chief Executive Officer since 2024

MD, MA, MS

Dr. Vicki LoPachin

Icahn School of Medicine at Mount Sinai

Chief Medical Officer

MD, FACP, MBA

Findings from Research

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]

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]

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]

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Homework "Dose," Type, and Helpfulness as Predictors of Clinical Outcomes in Prolonged Exposure for PTSD. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Associability-modulated loss learning is increased in posttraumatic stress disorder. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Evaluating web-based cognitive-affective remediation in recent trauma survivors: study rationale and protocol. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Altered reward processing in the nucleus accumbens and mesial prefrontal cortex of patients with posttraumatic stress disorder. [2014]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

Associations of psychotherapy dose and SSRI or SNRI refills with mental health outcomes among veterans with PTSD. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

Intact error monitoring in combat Veterans with post-traumatic stress disorder. [2018]

8. Switzerland 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. [2023]

9. Italy pubmed.ncbi.nlm.nih.gov

Trauma exposure acutely alters neural function during Pavlovian fear conditioning. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Neurocomputational Changes in Inhibitory Control Associated With Prolonged Exposure Therapy. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Cognitive dysfunctions associated with PTSD: evidence from World War II prisoners of war. [2008]

12. England pubmed.ncbi.nlm.nih.gov

Cumulative trauma load and timing of trauma prior to military deployment differentially influences inhibitory control processing across deployment. [2023]