Obstructive Sleep Apnea
Conditions
Brief summary
Obstructive sleep apnea (OSA) is common and has major health implications but treatment options are limited. OSA patients show a marked reduction in upper airway (UA) dilator muscle activity at sleep onset and this phenomenon leads to increased collapsibility of UA compared to normal subjects. In this protocol the investigators will test the effect of LTM1201L, LTM1201LN, LTM1201LB, LTM1201LD administered before sleep on OSA phenotype traits and OSA severity during sleep.
Interventions
DRUGPlacebo oral capsule
Placebo capsule before sleep
DRUGLTM1201L
LTM1201L capsule before sleep
DRUGLTM1201LN
LTM1201LN capsule before sleep
DRUGLTM1201LB
LTM1201LB capsule before sleep
DRUGLTM1201LD
LTM1201LD capsule before sleep
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* AHI \> 10 events/h during NREM supine sleep
Exclusion criteria
* Any medical condition other than well controlled hypertension and mild diabetes. * Any medication known to influence breathing, sleep/arousal, or muscle physiology. * Claustrophobia. * Inability to sleep supine. * Allergy to any of the medications tested in the protocol. * History of kidney stones, hypercalcemia, primary hyperparathyroidism, sarcoidosis, hypervitaminosis D. * Individuals with underlying cardiac disease, such as arrhythmias. * Individuals taking psychiatric medications, such as an MAO-I, SSRI or SNRI, or any of the studied medications for medical care. * For women: Pregnancy. * Pulmonary hypertension * Severe OSA with a mean SaO2 lower than 88%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apnea Hypopnea Index (AHI, Average Number of Events for Every Hour of Sleep) | 1 night | Based on previous studies the investigators anticipate that active comparators will reduce AHI more effectively in subjects with moderate sleep apnea and low-to-moderate collapsibility (Vpassive \>50% of eupneic values). Higher AHI indicates more severe OSA, usually ranging between 10 to 110 events/hour. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Collapsibility of the Upper Airway: VActive (L/Min) | 1 night | VActive: ventilation when ventilatory drive is high and pharyngeal dilator muscles are relatively active. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Analyzed Participants All participants who were randomized, completed both study nights, and were included in the analysis. | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Analyzed Participants |
|---|---|
| Age, Continuous | 50.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 3 / 6 | 5 / 6 | 5 / 6 | 3 / 5 | 5 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Apnea Hypopnea Index (AHI, Average Number of Events for Every Hour of Sleep)
Based on previous studies the investigators anticipate that active comparators will reduce AHI more effectively in subjects with moderate sleep apnea and low-to-moderate collapsibility (Vpassive \>50% of eupneic values). Higher AHI indicates more severe OSA, usually ranging between 10 to 110 events/hour.
Time frame: 1 night
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Apnea Hypopnea Index (AHI, Average Number of Events for Every Hour of Sleep) | 20.8 events/hour of sleep | Standard Error 8 |
| LTM1201L | Apnea Hypopnea Index (AHI, Average Number of Events for Every Hour of Sleep) | 24.4 events/hour of sleep | Standard Error 11.3 |
| LTM1201LN | Apnea Hypopnea Index (AHI, Average Number of Events for Every Hour of Sleep) | 18.8 events/hour of sleep | Standard Error 11.3 |
| LTM1201LB | Apnea Hypopnea Index (AHI, Average Number of Events for Every Hour of Sleep) | 14 events/hour of sleep | Standard Error 11.3 |
| LTM1201LD | Apnea Hypopnea Index (AHI, Average Number of Events for Every Hour of Sleep) | 9.1 events/hour of sleep | Standard Error 11.9 |
Comparison: mean difference vs Placebop-value: >0.5Mixed Models Analysis
Comparison: mean difference vs Placebop-value: >0.5Mixed Models Analysis
Comparison: mean difference vs Placebop-value: >0.5Mixed Models Analysis
Comparison: mean difference vs Placebop-value: 0.33Mixed Models Analysis
Secondary
Collapsibility of the Upper Airway: VActive (L/Min)
VActive: ventilation when ventilatory drive is high and pharyngeal dilator muscles are relatively active.
Time frame: 1 night
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Collapsibility of the Upper Airway: VActive (L/Min) | 2.657 Liters/minute | Standard Error 0.6865 |
| LTM1201L | Collapsibility of the Upper Airway: VActive (L/Min) | 3.856 Liters/minute | Standard Error 1.04 |
| LTM1201LN | Collapsibility of the Upper Airway: VActive (L/Min) | 3.822 Liters/minute | Standard Error 1.049 |
| LTM1201LB | Collapsibility of the Upper Airway: VActive (L/Min) | 6.008 Liters/minute | Standard Error 1.11 |
| LTM1201LD | Collapsibility of the Upper Airway: VActive (L/Min) | 3.091 Liters/minute | Standard Error 1.161 |
p-value: 0.12Mixed Models Analysis