Models of Auditory Hallucination
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04210557 |
|
Recruitment Status :
Recruiting
First Posted : December 24, 2019
Last Update Posted : March 16, 2021
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Schizophrenia Schizo Affective Disorder Auditory Hallucination | Device: Transcranial Magnetic Stimulation (TMS) | Not Applicable |
Hallucinations are percepts without stimulus. 70% of patients with schizophrenia suffer distressing auditory hallucinations. Their mere presence increases the risk of suicide. Most reach remission with D2 dopamine receptor blocking drugs after 1 year of adherence. However, 30% of patients have intractable hallucinations, and 50% are non-adherent to their medications, commonly because of unfavorable side-effects - those intractable and non-adherent patients continue to suffer. There is a clear need for a mechanistic understanding of hallucinations as a prelude to rational treatment design.
This study provides the initial steps towards the development of an interventional biomarker for clinical hallucinations, grounded in computational neuroscience.
Computational psychiatry involves harnessing the power of computational neuroscience to address the clinical needs of those suffering from serious mental illnesses. There has been much discussion of the promise of the approach. There have been few studies thus far and they have largely involved correlative methods like functional neuroimaging. This study will address this shortcoming by causally manipulating the neural loci of computational model parameters in-person in patients with psychosis using transcranial magnetic stimulation (TMS), tracking the impact of this manipulation on behavioral task performance . With such a causal intervention, the veracity of the model's explanation of hallucinations will be either validated or disconfirmed. If validated, the model can be further developed as a biomarker for predicting the hallucination onset, guiding, developing or tracking the effects of treatments for hallucinations. If disconfirmed, the model ought to be discarded and other alternatives should be pursued.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 100 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Masking Description: | The participant, the physician administering TMS, and the research psychologist will be blind to the condition. One research assistant will be unblinded to the condition. This unblinded research assistant is responsible for setting up the active TMS coils or the sham TMS coils and determining the protocol used, to maintain the blindness of other study staff and the participant. |
| Primary Purpose: | Basic Science |
| Official Title: | Models of Auditory Hallucination |
| Actual Study Start Date : | February 27, 2020 |
| Estimated Primary Completion Date : | June 30, 2021 |
| Estimated Study Completion Date : | June 30, 2022 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: TMS to insula
This study will recruit 30 clinical voice hearers (P+H+). They will complete two parallel forms of the conditioned hallucinations task (with different visual and auditory stimuli) on two occasions, separated by a week. TMS and sham will be delivered in a randomized counterbalanced order. Hypothesis: Inhibiting the insula will decrease prior over-weighting. If this computational perturbation is responsible for conditioned hallucinations, then ameliorating it with TMS that increases insula engagement will decrease conditioned hallucination responses. Furthermore, the prior weighting parameter will be reduced following active TMS compared with sham. |
Device: Transcranial Magnetic Stimulation (TMS)
Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction. An electric pulse generator, or stimulator, is connected to a magnetic coil, which in turn is connected to the scalp. The stimulator generates a changing electric current within the coil which induces a magnetic field; this field then causes a second inductance of inverted electric charge within the brain itself.
Other Name: repetitive transcranial magnetic stimulation (rTMS) |
|
Experimental: TMS to cerebellum
This study will recruit a further 70 clinical voice hearers. Again, they will complete parallel forms of the conditioned hallucinations task on two occasions, separated by a week. They will receive excitatory TMS over the cerebellum (and sham on the other occasion, in a randomized counterbalanced order). Hypotheses: Exciting the cerebellum will increase belief-updating. If poor belief-updating contributes to conditioned hallucinations, increasing cerebellum engagement should decrease conditioned hallucinations and alter the belief-updating model parameter compared with sham TMS.
|
Device: Transcranial Magnetic Stimulation (TMS)
Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction. An electric pulse generator, or stimulator, is connected to a magnetic coil, which in turn is connected to the scalp. The stimulator generates a changing electric current within the coil which induces a magnetic field; this field then causes a second inductance of inverted electric charge within the brain itself.
Other Name: repetitive transcranial magnetic stimulation (rTMS) |
- Conditioned Hallucinations task performance [ Time Frame: 18 months ]The primary outcome measure is the number of times participants report hearing tones that were not presented. There are 360 total trials. There are 120 no tone trials. People who hear voices typically report hearing tones on 30% of the no tone trials (approximately 36 times, as compared to 12 times in people who do not hear voices). The investigators anticipate fewer conditioned hallucinations (fewer than 36 reports of tones when none were presented) in the active TMS conditions as compared to the sham.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 45 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Aged 18 - 45 years
- Voice hearing patients
- Meet diagnostic criteria for DSM-V schizophrenia or schizophreniform disorder
- Report hearing voices at least once a day
- Score > 3 on PANSS P3 (hallucinations item)
Exclusion Criteria:
- DSM-V substance use disorder within the past 6 months
- Previous head injury with neurological symptoms and/or unconsciousness
- Intellectual disability (IQ < 70)
- Non-English speaker
-
Contraindications for TMS, including:
- History of seizures
- Metallic implants
- Pacemaker
- Pregnancy
- Less than 6 weeks of a stable dose of psychotropic medication(s)
- Comorbid mood or anxiety diagnosis
- Clinically/behaviorally instability and unable to cooperate with TMS procedures
- Clinically significant medical condition(s)
- Unstable medical condition(s) based on EKG, medical history, physical examination, and routine lab work
- Personal history of stroke
- Family history of seizures
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04210557
| Contact: Ramone Brown, BA | 203 974 7866 | belieflab@yale.edu |
| United States, Connecticut | |
| Connecticut Mental Health Center (CMHC) | Recruiting |
| New Haven, Connecticut, United States, 06519 | |
| Contact: Kyle Pedersen, MAR 203-974-7089 kyle.pedersen@yale.edu | |
| Contact: Norma Gibson, MEd (203)974-7089 norma.gibson@yale.edu | |
| Sub-Investigator: Al Powers, PhD, MD | |
| Principal Investigator: | Philip R Corlett, PhD | Yale School of Medicine |
| Responsible Party: | Yale University |
| ClinicalTrials.gov Identifier: | NCT04210557 |
| Other Study ID Numbers: |
2000023640 |
| First Posted: | December 24, 2019 Key Record Dates |
| Last Update Posted: | March 16, 2021 |
| Last Verified: | March 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | Yes |
| Product Manufactured in and Exported from the U.S.: | No |
|
TMS Transcranial Magnetic Stimulation |
|
Hallucinations Schizophrenia Mood Disorders Psychotic Disorders Schizophrenia Spectrum and Other Psychotic Disorders |
Mental Disorders Perceptual Disorders Neurobehavioral Manifestations Neurologic Manifestations Nervous System Diseases |