Trial of Stimulus-response Potentiation in Schizophrenia

Pilot Trial of Stimulus-response Potentiation in Schizophrenia

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

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Diagnostic test: Auditory High Frequency Tetanizing Stimulation; Diagnostic test: Sham Comparator

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo Governerate
    • Cairo, Cairo Governerate, Egypt, 11562
      • Department of Psychiatry-Faculty of medicine-University of Cairo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

For Schizophrenia group:

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.

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:

Inclusion criteria:

• 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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Schizophrenia TS+ve; Schizophrenia patients who receive auditory high frequency Tetanizing Stimulation	Diagnostic test: Auditory High Frequency Tetanizing Stimulation; 50 ms tone pips presented at high frequency for 120 seconds
SHAM_COMPARATOR: Schizophrenia TS-ve; Schizophrenia patients who receive sham comparator	Diagnostic test: Sham Comparator; auditory tone pips with interstimulus interval (ISI) 1 sec
EXPERIMENTAL: Control TS+ve; Healthy controls who receive auditory high frequency Tetanizing Stimulation	Diagnostic test: Auditory High Frequency Tetanizing Stimulation; 50 ms tone pips presented at high frequency for 120 seconds
SHAM_COMPARATOR: Control TS-ve; Healthy controls who receive sham comparator	Diagnostic test: Sham Comparator; auditory tone pips with interstimulus interval (ISI) 1 sec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
N100 wave (AEP) amplitude in µv [microvolts]	N100 or N1 is a large, negative-going evoked potential measured by electroencephalography. It peaks in adults between 80 and 120 milliseconds after the onset of a stimulus, and distributed mostly over the fronto-central region of the scalp.	1-2 hours
P300 wave amplitude in µv [microvolts] (auditory odd-ball task)	The P300 (P3) wave is an event related potential (ERP) component elicited in the process of decision making. It is considered to be an endogenous potential, as its occurrence links not to the physical attributes of a stimulus, but to a person's reaction to it. More specifically, the P300 is thought to reflect processes involved in stimulus evaluation or categorization.	1-2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
performance of Wisconsin Card Sorting test (WCST).	Wisconsin Card Sorting Test (WCST) is a neuropsychological test of "set-shifting", i.e. the ability to display flexibility in the face of changing schedules of reinforcement.	3 days

Collaborators and Investigators

• Sponsor: Cairo University
• Collaborators: University of Pittsburgh
• Investigators: Study Director: Ola O Shahin, MD, Department of Psychiatry-University of Cairo; Study Director: Vishwajit L Nimgaonkar, PhD, Department of Psychiatry-University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2019
• Primary Completion (ACTUAL): April 15, 2021
• Study Completion (ACTUAL): April 15, 2021

Study Registration Dates

• First Submitted: March 25, 2019
• First Submitted That Met QC Criteria: March 26, 2019
• First Posted (ACTUAL): March 27, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 1, 2021
• Last Update Submitted That Met QC Criteria: June 29, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: N-173-2019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No