Trial of Stimulus-response Potentiation in Schizophrenia

NCT ID: NCT03892876

Last Updated: 2021-07-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-01
• Study Completion Date: 2021-04-15

Brief Summary

This clinical trial aims at examining the effects of auditory high-frequency stimulation in schizophrenia patient, aiming to increase their AEPs, which are known to be attenuated from previous literature

Detailed Description

Schizophrenia is a chronic psychiatric disorder with a lifetime prevalence of 4.0 per 1,000. The introduction of antipsychotic medications in the 1950s resulted in marked clinical improvement in the symptom profile of schizophrenia, nevertheless the disease still contributes to a significant proportion of global disease burden in terms of both morbidity and mortality. In this regard, cognitive deficits and residual negative symptoms are considered major contributing factors to psychosocial disability and poor functional outcome associated with the disorder.

Higher-order cognitive functions; e.g. working memory and executive functions; show variable deficits and are considered a core clinical symptom of schizophrenia. On the other hand, the disorder is also characterized by abnormalities at the basic level of primary sensory processing, i.e. auditory, visual and somatosensory processing. Such abnormalities in the primary process of sensory perception could change the sensory experiences of schizophrenia patients and thus contribute to the psychopathology.

Event-related potentials (ERPs) are the neurophysiological correlates of sensory processing. ERP abnormalities have been widely described in schizophrenia literature: Pre-pulse inhibition of startle (PPI) in which a weaker pre-stimulus (pre-pulse) inhibits the reaction to a subsequent strong startling stimulus (pulse) is impaired in schizophrenia. P50 suppression, a measure of sensory gating, is also often absent or reduced in the disorder. N100; a measure of basic auditory sensory perception; shows significant amplitude reduction in patients compared to controls. Mismatch negativity (MMN), a measure of automatic deviance detection and shows characteristic attenuation in schizophrenia. P300, which is involved in higher-level stimulus evaluation and categorization, also shows abnormalities along the disease course.

In the study by Clapp et al., 2005, auditory high frequency stimulation (tetanizing stimulation) resulted in an increase in auditory-evoked potentials (AEPs) in healthy individuals; i.e. an increase in N1 amplitude that persisted even after stimulation. This augmentation of N1 amplitude was regarded as a result of plastic synaptic potentiation similar to long-term potentiation (LTP) described after electrical tetanic stimulation in cellular studies. Similar findings were later replicated by Lei et al., 2017, where they used pure tones, narrow band noises and white noise to induce stable potentiation and augmentation of N1 amplitude.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Schizophrenia TS+ve

Schizophrenia patients who receive auditory high frequency Tetanizing Stimulation

Group Type: EXPERIMENTAL

Auditory High Frequency Tetanizing Stimulation

Intervention Type: DIAGNOSTIC_TEST

50 ms tone pips presented at high frequency for 120 seconds

Schizophrenia TS-ve

Schizophrenia patients who receive sham comparator

Group Type: SHAM_COMPARATOR

Sham Comparator

Intervention Type: DIAGNOSTIC_TEST

auditory tone pips with interstimulus interval (ISI) 1 sec

Control TS+ve

Healthy controls who receive auditory high frequency Tetanizing Stimulation

Group Type: EXPERIMENTAL

Auditory High Frequency Tetanizing Stimulation

Intervention Type: DIAGNOSTIC_TEST

50 ms tone pips presented at high frequency for 120 seconds

Control TS-ve

Healthy controls who receive sham comparator

Group Type: SHAM_COMPARATOR

Sham Comparator

Intervention Type: DIAGNOSTIC_TEST

auditory tone pips with interstimulus interval (ISI) 1 sec

Interventions

Auditory High Frequency Tetanizing Stimulation

50 ms tone pips presented at high frequency for 120 seconds

Intervention Type: DIAGNOSTIC_TEST

Sham Comparator

auditory tone pips with interstimulus interval (ISI) 1 sec

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Able to give written informed consent
• Males (ages 20-50 years)
• Diagnosis of schizophrenia as confirmed by Structured Clinical Interview for DSM-V-TR (SCID)
• on stable doses of antipsychotic medications for at least 15 days
• scores 4 or more on at least one item of the Positive and Negative Syndrome Scale.

• able to give written informed consent
• males (ages 20-50).

Exclusion Criteria

• History of / or current medical/neurological illnesses e.g. mental retardation (DSM-V) or epilepsy or significant head trauma
• Any type of hearing deficit will be excluded by audiometry assessment
• Substance abuse in the past 2 months
• medical conditions that make it difficult for the patient to visit the clinic in the designed schedule.

For control group:

• History of / or current medical/neurological illnesses e.g. mental retardation (DSM-V) or epilepsy or significant head trauma
• Any type of hearing deficit
• if they meet any axis-I diagnosis according to DSM-V confirmed by SCID.
• scores 2 or more on one item of the Positive and Negative Syndrome Scale

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Pittsburgh

OTHER

Sponsor Role: collaborator

Cairo University

OTHER

Sponsor Role: lead

Responsible Party

Kyrillos Meshreky

Assistant lecturer of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ola O Shahin, MD

Role: STUDY_DIRECTOR

Department of Psychiatry-University of Cairo

Vishwajit L Nimgaonkar, PhD

Role: STUDY_DIRECTOR

Department of Psychiatry-University of Pittsburgh

Locations

Department of Psychiatry-Faculty of medicine-University of Cairo

Cairo, Cairo Governerate, Egypt

Countries

Egypt

Other Identifiers

N-173-2019

Identifier Type: -

Identifier Source: org_study_id