Prepulse Inhibition Test

“At the screening visit medical history, exam, vital signs, laboratory testing including routine chemistries, blood counts, thyroid functions, electrocardiogram (ECG), and a pregnancy test (females) were evaluated, and baseline CPT (Carolina Project Fragile X continuous performance test) and prepulse inhibition (PPI) outcome measures were obtained.”

“baseline CPT (Carolina Project Fragile X continuous performance test) and prepulse inhibition (PPI) outcome measures were obtained”

“baseline CPT (Carolina Project Fragile X continuous performance test) and prepulse inhibition (PPI) outcome measures were obtained”

“At the treatment visit, 14–28 days after screening, an IV was inserted for blood drawing and the subject received the study medication orally. The first subject for each gender was dosed with 50 mg fenobam, the second with 100 mg, and all subsequent subjects with 150 mg.”

“Blood for pharmacokinetic testing, blood pressure, heart rate and side effect screening was obtained at 0, 15, 30, 45, 60, 120, 180, 240, 300, and 360 min after dosing.”

“Our side effects screening protocol involved asking both the subject and family members if the subject was having any of a structured list of symptoms relevant to potential effects of fenobam (aggression, fatigue, hyperactivity, anxiety and fidgetiness, increase in self stimulation, odd behaviour, inappropriate laughter, dizziness, vertigo, nausea, paraesthesia, and headache), and direct observation by the physician and family for the above symptoms and other behavioural changes.”

“Post-treatment PPI was performed after the 60 min blood sampling, followed by CPT.”

“Startle stimuli (SS) were 50 ms 105 db SPL white noise pulses and acoustic prepulses (PP) are 25 ms 75 db SPL 1 kHz tones. These trials are delivered while participants watch a silent movie to maintain compliance and interest in the procedure. resulting in a protocol with 30 total trials (10 with SS alone, 10 with 120 ms prepulse and 10 with 240 ms prepulse)”

“10 with 120 ms prepulse and 10 with 240 ms prepulse. PPI at 120 ms has excellent test-retest reliability with intraclass correlations of 0.85 for FXS and 0.88 for controls”

“Test-retest studies have demonstrated good to excellent reliability for PPI at 120 ms and 240 ms, but inadequate reliability for PPI at 60 ms. Therefore, for the current study, we eliminated the 60 ms trial type and added two trials per type, resulting in a protocol with 30 total trials”

“Digitised obicularis oculi electromyographic peak magnitudes recorded between 20 ms and 200 ms post startle probe onset were averaged across trials within each type.”

“Post-treatment PPI was performed after the 60 min blood sampling, followed by CPT. the number of correct hits on a target stimuli, omissions involving lack of reaction to a target (attention deficit), and commissions involving reacting to a non-target (impulsivity, poor inhibitory control) were tabulated.”

“Fenobam concentrations from plasma samples were measured with MS-MS based assays validated for human application, using positive ion liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). For comparison, plasma samples over 24 h were obtained from three healthy adult male volunteers.”