Explorative Study for Treating Persistent Developmental Stuttering With Ramipril

NCT04173949 | Active Not Recruiting Phase 3

• 1 other identifier: EMC169-15
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief 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. 1.Stuttering is associated with high striatum dopamine levels
2. 2.Angiotensin receptors are present in the striatum
3. 3.Angiotensin causes elevated striatum dopamine levels
4. 4.ACE inhibitors penetrate the blood brain barrier and reduce brain angiotensin II levels.
5. 5.The MINI Neuropsychiatric interview will be used to rule out major neuropsychiatric conditions
6. 6.Stuttering evaluation
7. 7.Stuttering Severity instrument Version 4 (SSI-4) (Riley 2009)
8. 8.SLD :Percentage of stuttered syllables (Yairi 2015)
9. 9.The Subjective Screening of Stuttering (SSS)
10. 10.Speech Situation Checklist (Brutten 1975,1981)
11. 11.Leibowitz Social Anxiety Scale (Leibowitz 1987)
12. 12.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.
13. 13.Orthostatic hypotension will be defined as a drop of 20mmHg systolic or 10mmHg diastolic, one and three minutes after standing from sitting position.
14. 14.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)

Conditions

Persistent Developmental Stuttering

Outcome Measures

Primary Outcomes (1)

• changed in stuttered syllables

  The difference in stuttering measures with and without treatment will be determined.

  4 month

Study Arms (1)

Ramipril 2.5 MG

EXPERIMENTAL

Ramipril 2.5 MG orall, daily.

Drug: Ramipril 2.5 MG

Interventions

Ramipril 2.5 MG DRUG

3 month of treatment with daily Ramipril 2.5 MG

Ramipril 2.5 MG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 or above
• Developmental stuttering of 10 points severity at least (SSI-4)
• Agree not to have any speech or emotional therapy during the trial.

You may not qualify if:

• Systolic blood pressure \< 110mmHg
• Estimated creatinine clearance \< 50ml/min
• Baseline potassium \> 5meq/ml
• Any sign of psychopathology by the MINI international neuropsychiatric interview
• Any psychotropic medications or substances in the past month
• History of angioedema or cough with any ACE inhibitor
• Aliskerin use in diabetes patients
• Current medication include ACE inhibitors or ARBS
• Pregnancy, or pregnancy plans during the study
• Less than 3% stuttered syllables
• Subjects with cluttering-stuttering when the cluttering is prominent

Sponsors & Collaborators

• HaEmek Medical Center, Israel: lead

Study Sites (2)

Haemek Medical Center

Afula, Israel

Location

Asaf Harophe

Tzrifin, Israel

Location

MeSH Terms

Interventions

Ramipril

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study will begin as a pilot study in which 10 stuttering patients will be recruited for 12 weeks on open label Ramipril 2.5mg.

Study Record Dates

• First Submitted: November 7, 2019
• First Posted: November 22, 2019
• Study Start: March 15, 2020
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: March 13, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IL (2)