Impact of Exogenous Ketones on Sleep Disruption in Vulnerable Populations: Phase I Study (KETO-SLEEP 1)
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Beta hydroxybutyrate (BHB) maximal concentration (Cmax)
研究概览
简要总结
Obstructive Sleep Apnea (OSA) is a common medical disorder that is associated with reduced quality of life and higher risk of cardiovascular disease. Treatments for OSA and limited and not well tolerated. Our lab has shown that a low carbohydrate, high fat ketogenic diet (KD) can reduce OSA severity. Since it can be challenging to adhere to a ketogenic diet, the investigators propose that ingesting exogenous ketones can be an alternative method to improve OSA. Specifically the investigators will examine the effect of taking a commercially available product (Ketone-IQ) at bedtime on overnight ketones and sleep quality. The investigators will also examine the effect of Ketone-IQ on sleep apnea severity, compared to placebo.
This project will examine the pharmacokinetics, tolerability, and sleep impacts of ingesting exogenous ketones before sleep in patients with sleep apnea, while under treatment for OSA.
[Aim 2: Examine the preliminary efficacy of ingesting exogenous ketones before sleep on OSA]
详细描述
Sleep is a vulnerable period during which blunted respiratory drive and low airway muscle tone can cause dangerous breathing disorders. Obstructive sleep apnea (OSA) describes the intermittent collapse of the upper airway that induces O2 desaturations and arousals from sleep, placing patients at risk for cardiovascular disease, stroke, and death. In some obese patients, sleep causes carbon dioxide (CO2) accumulation progressing to daytime hypercapnia, a condition called obesity hypoventilation syndrome (OHS). Continuous positive airway pressure (CPAP) treats OSA and OHS, but is poorly tolerated, and may not fully correct sleep dysfunction.
Changes in metabolism may help to control OSA or OHS. The investigators recently published results from the Ketogenic Diet for OHS clinical trial (KETOHS, NCT04108819) showing that a 2-week ketogenic diet (high fat, low carbohydrate) for patients with OSA and OHS lowered reduced CO2, serum bicarbonate (HCO3), respiratory quotient, nocturnal hypoxemia(2). KD also significantly improved OSA. After participants resumed their prior diet, CO2 returned to baseline. The mechanisms by which KD improves sleep in this population could be related to reduced CO2 production (through fat oxidation), lowering of body weight, or direct effects of ketone bodies on sleep and breathing.
It is difficult to adhere long-term to KD, and there are multiple effects of this diet that make it challenging to understand mechanistic impacts on respiration. The investigators hypothesize that increasing ketone levels in the body, without having to adhere to a ketogenic diet, may be another method to improve breathing during sleep. Indeed, some drugs affecting acid-base status (e.g. acetazolamide or sulthiame) improve OSA, presumably through increasing and stabilizing respiratory drive. In this pilot study, the investigators will examine the pharmacokinetics, tolerability, and impacts of ingesting exogenous ketones (which are commercially available products) on sleep and breathing.
The specific ketone product to be tested for its impact on sleep and breathing is 1,3 butanediol (1,3BD) in a commercially available formulation called "Ketone IQ". 1,3BD is converted by liver metabolism into the ketone body beta-hydroxybutyrate (BHB) and has been utilized in multiple studies.
This project will be conducted in two studies, KETO-SLEEP 1 (KS1), and KETO-SLEEP 2 (KS2).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 18-65 years old with a BMI of 18 - 35 kg/m2
- •History of moderate-severe OSA as defined by AHI >15 events/hr (American Academy of Sleep Medicine criteria),
- •Adherent to CPAP (objectively determined via device download over last 30 days) using CPAP at least 70% of days for >=4 hours.
- •CPAP pressure ≤10 cm water (H2O) (based on prescribed CPAP pressure, or median pressure on an auto-titrating CPAP device).
排除标准
- •No concomitant sleep disorder (such as insomnia, restless leg syndrome, narcolepsy, idiopathic hypersomnia)
- •No current daytime respiratory impairment such as uncontrolled asthma, or uncontrolled chronic obstructive pulmonary disease (COPD), pneumonia, interstitial lung disease.
- •No use of supplemental oxygen.
- •Currently on a low carbohydrate (<130 g carbohydrate/day) or ketogenic diet, intermittent fasting, or consuming exogenous ketones
- •Pregnancy or breastfeeding
- •Alcohol consumption of > 10 standard drinks per week
- •Use of nightly medications that affect breathing (e.g. opiates, acetazolamide)
- •Use of Sodium-glucose cotransporter-2 (SGLT2) inhibitors. For example, Canagliflozin (Invokana), Dapagliflozin (Farxiga), Empagliflozin (Jardiance), Ertugliflozin (Steglatro)
研究组 & 干预措施
Ketone Intervention
Participants with sleep apnea using CPAP will undergo open-label procedures. They will ingest (1) nothing, (2) Ketone IQ 20 g or (3) Ketone IQ 40 g before bedtime and undergo objective and subjective sleep assessments.
干预措施: Ketone-IQ (1,3 Butanediol) (Dietary Supplement)
结局指标
主要结局
Beta hydroxybutyrate (BHB) maximal concentration (Cmax)
时间窗: Night 2, Night 5
Participants will measure their capillary BHB levels at home at 4 time points after ingestion (1, 3, 5 hours, and final awakening). The investigators will derive the maximal BHB concentration (mmol) of these timepoints. Measured on two occasions: Night 2 (Ketone IQ 20 g) and Night 5 (Ketone IQ 40 g).
次要结局
未报告次要终点