Clinical Trial Summary
Persistent developmental stuttering (PDS) is diagnosed when developmental stuttering persists
beyond adolescence. Most stutterers experience vast improvement in stuttering during
childhood and it generally disappears within five years. A minority of stutterers continue
stuttering over age 18, often accompanied by social and personal difficulties.
Following a report of a 75 year old woman, with severe Persistent developmental stuttering ,
who experienced significant improvement in her stuttering since treated by Ramipril for
hypertension, we scrutinized the literature, and discovered that there is a physiological
basis for this surprising reaction. Ace inhibitors, such as Ramipril, might in fact be
successful for treating Persistent developmental stuttering .
In theory, it seems that ACE inhibitors, such as Ramipril could improve stuttering by
reducing striatum dopamine levels.
1. Stuttering is associated with high striatum dopamine levels
2. Angiotensin receptors are present in the striatum
3. Angiotensin causes elevated striatum dopamine levels
4. ACE inhibitors penetrate the blood brain barrier and reduce brain angiotensin II levels.
Methods The study will begin as a pilot study in which 10 stuttering patients will be
recruited for 12 weeks on open label Ramipril 1.25mg/d.
If there is improvement in at least 2 of the stuttering patients, we will continue to the
main study.
Efficacy Evaluation:
1. The MINI Neuropsychiatric interview will be used to rule out major neuropsychiatric
conditions
2. Stuttering evaluation
1. Stuttering Severity instrument Version 4 (SSI-4) (Riley 2009)
2. SLD :Percentage of stuttered syllables (Yairi 2015)
3. The Subjective Screening of Stuttering (SSS)
4. Speech Situation Checklist (Brutten 1975,1981)
3. Leibowitz Social Anxiety Scale (Leibowitz 1987)
The efficacy evaluation will be performed by speech therapists. All evaluations will be will
be recorded on video
Safety evaluation:
1. Blood pressure: The average of three consecutive measures. Blood pressure will be
measure in both arms on the first meeting, and thereafter on the arm with the highest
measurements.
2. Orthostatic hypotension will be defined as a drop of 20mmHg systolic or 10mmHg
diastolic, one and three minutes after standing from sitting position.
3. Creatinine clearance will be calculated by the MDRD method (Levy 2006) GFR, in mL/min
per 1.73 m2 = 186.3 x SCr (exp[-1.154]) x Age (exp[-0.203]) x (0.742 if female) x (1.21
if black)
