Role of Enhancing Serotonin Receptors Activity for Sleep Apnea Treatment in Patients With SCI

NCT02458469 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: NURC-062-12S1IK2CX000547
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to look at the effect of exciting using drugs to target a specific pathway in the body, that relies on a natural chemical the body produces called 'serotonin', in patients with spinal cord injury (SCI) during sleep. During this part of the study participants will be asked to take buspirone (Buspar) (15-50mg per day), trazodone (100mg per day) and a placebo in a random fashion, each for a 2 week period (drug period) of time followed by two weeks without drugs (washout period). The drugs will not be taken all at the same time, but each will be taken separately for two weeks followed by a night study to look at the effect the medication/placebo pill has on the way the body responds during sleep.

Conditions

Spinal Cord Injury; Sleep Disordered Breathing

Outcome Measures

Primary Outcomes (1)

• CO2 Reserve (Delta-PETCO2-AT)

  Randomized placebo-controlled cross-over study. Each subject was studied on three separate occasions: (1) Buspirone vs. Trazodone vs. placebo for 2 weeks; After the two-week treatment a noninvasive nasal mechanical ventilation study was repeated to determine the hypocapnic apneic threshold. (2) Cross over medication for two weeks was followed by a second noninvasive nasal mechanical ventilation study to determine the CO2 reserve (Delta-PETCO2-AT) and hypocapnic apneic threshold followed by two weeks washout. (3) Cross over medication for two weeks was followed by another sleep study to determine the hypocapnic apneic threshold.

  Two weeks

Secondary Outcomes (1)

• Apnea-Hypopnea Index (AHI)

  Two weeks

Study Arms (3)

Buspirone

ACTIVE COMPARATOR

This drug will be taken for two week period

Drug: Buspirone

Trazodone

ACTIVE COMPARATOR

This drug will be taken for two week period

Drug: Trazodone

Placebo

PLACEBO COMPARATOR

A placebo pill will be taken at bed time for two week period

Drug: Placebo

Interventions

Buspirone DRUG

The initial dose of Buspirone is 15 mg daily (7.5 mg bid.). To achieve an optimal therapeutic response, at intervals of 2 to 3 days the dosage may be increased 5 mg per day until a maximum dose 30mg/day is reached.

Buspirone

Trazodone DRUG

100 mg dose before bed-time

Trazodone

Placebo DRUG

One placebo pill before bed-time

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults with SCI (\>6months after spinal cord injury) at the T6 level/above

You may not qualify if:

• Pregnant and lactating females
• Heart failure, vascular disease, or stroke
• Advanced chronic obstructive pulmonary disease (COPD), liver disease, and chronic kidney disease
• BMI \>38 kg/m2
• Mechanical ventilation dependence
• The following medications are not allowed (potential interaction with buspirone or inhibition of the CYP3A4 system):
• cimetidine
• ketoconazole
• ritonavir
• itraconazole
• erythromycin
• diltiazem
• verapamil
• Monoamine oxidase (MAO) inhibitors \[such as Marplan, Nardil, Parmate, Emsam\]
• Other prohibited concomitant medications include haloperidol, trazodone, or triazolam

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

John D. Dingell VA Medical Center, Detroit, MI

Detroit, Michigan, 48201, United States

Location

MeSH Terms

Conditions

Spinal Cord Injuries; Sleep Apnea Syndromes

Interventions

Buspirone; Trazodone

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders

Intervention Hierarchy (Ancestors)

Spiro Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Polycyclic Compounds; Pyridones; Pyridines

Limitations and Caveats

* The sample size is small and the majority are males, therefore findings from this study may not be applicable to the general population * The study required heavy instrumentation which may have affected natural sleep

Results Point of Contact

• Title: Dr. Abdulghani Sankari Principal Investigator
• Organization: JOHN D DINGELL VA MEDICAL CENTER

abdulghani.sankari@va.gov

13135761000

Study Officials

• Abdulghani Sankari, MD PhD

  John D. Dingell VA Medical Center, Detroit, MI

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2015
• First Posted: June 1, 2015
• Study Start: May 14, 2015
• Primary Completion: April 12, 2019
• Study Completion: April 12, 2019
• Last Updated: June 14, 2021
• Results First Posted: April 9, 2020

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)