Phase 2
N=22
Abnormal Ventilatory Response to Carbon Dioxide: a Potential Biomarker for Seizure Induced Respiratory Depression & Modification by SSRI
Epilepsy · SUDEP
Bottom Line
View on ClinicalTrials.gov: NCT02929667 ↗Enrolled (actual)
22
Serious AEs
0.0%
Results posted
May 2020
Primary outcome: Primary: Study Recruitment Rate — 3.8 participants/3 months
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Fluoxetine (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Rup Kamal Sainju
- Primary completion
- Mar 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Study Recruitment Rate |
3.8 | — |
| PRIMARY Study Retention Rate |
1.2; 1.1 | — |
| SECONDARY Change in Minute Ventilation During Hypercapnic Ventilatory Response (HCVR) Testing |
1.739; 2.758 | — |
| SECONDARY Change in PHQ-9 Score. |
0.455; -1.000 | — |
| SECONDARY Change in Slope of HCVR |
-0.049; 0.072 | — |
Summary
Sudden unexpected death in epilepsy patients (SUDEP) is devastating outcome for some patients with epilepsy. It ranks second only to stroke among neurological diseases in years of potential life lost. Patho-mechanisms of SUDEP remain not well understood, however peri-ictal respiratory dysfunction likely plays an important role in many cases.
Literature supports a critical role for the serotonergic system in central control of ventilation. Serotonin neurons in the raphe nuclei of the brainstem sense rising carbon dioxide and low pH, thereby stimulating breathing and arousal. These responses may serve as mechanisms that protect against asphyxia, particularly during sleep or the post-ictal state. In mouse models of seizure-induced sudden death, pre-treatment with selective serotonin reuptake inhibitor (SSRI) agents prevents death following seizures. Hence, the investigators hypothesize that a subset of drug resistant epilepsy patients who have impaired central chemo-responsiveness have a greater degree of peri-ictal respiratory depression, therefore a higher risk of SUDEP. The investigators further hypothesize that fluoxetine will improve central chemo-responsiveness and therefore will reduce peri-ictal respiratory depression.
Eligibility Criteria
Inclusion Criteria
- Adult patients aged 18 or older
- Patients with epilepsy
- Native English speaker or adequate fluency in English to provide informed consent.
- Female patients of child-bearing potential must be using an acceptable method of contraception, and willing to refrain from sexual intercourse during the study.
Exclusion Criteria
- Progressive neurological disease.
- Clinical diagnosis of bipolar disease, panic disorder, psychosis or severe depression, or PHQ-9 score > 20
- Patients with prior hospitalization related to depression or Electroconvulsive therapy.
- History of suicidal ideation or intent in past or present
- Clinical history or laboratory evidence of hepatic or renal insufficiency.
- Pregnant or lactating women.
- Current heavy alcohol use (>14 drinks per week for men or >7 drinks per week for women) or) known medical disorder related to alcohol use or current illicit drug use, other than marijuana and its derivatives.
- Patients with recent use ( 2/week).
- History of a previous allergic reaction or adverse effects with fluoxetine, hypersensitive reaction-anaphylaxis; laryngeal edema; hives
- History of serotonin syndrome.
- History of uncontrolled pulmonary or cardiac illness.
- Patients with hypercapnic ventilatory response (HCVR) slope of > 2.0
- Patients with known prolong QT interval
- Patients with family history of prolong QT interval
- Patients with family history of sudden cardiac death under the age of 40 in a first degree relative.
Data sourced from ClinicalTrials.gov (NCT02929667). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.