HypoxiaPhase 4IH2NCT02058823
Intermittent Hypoxia 2: Cardiovascular and Metabolism
A Phase 4 study testing Valsartan and Amlodipine in people with Hypoxia and Sleep Apnea, run by University Hospital, Grenoble at 1 site in France.
Trial summary
The purpose of this study is to compare cardiovascular physiological adaptation to intermittent hypoxia (IH) of nonobese healthy subjects. The exposure will be two periods of two weeks (IH versus exposure "placebo hypoxia"). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Hypoxia, Sleep Apnea, Obstructive Sleep Apnea
- What is being tested?
- Valsartan and Amlodipine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteFrance
- Study dates
- 7 Aug 2013to 16 Mar 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy subject
- Subject aged of 18 years-old at least
- Diagnostic AHI<15/h and <5% of total sleep time spent with a SaO2<90%
- Free and informed consent signed
- Subject covered by social security
- Negative pregnancy test
Who cannot join
- Subject with a medical pathology (respiratory, cardiovascular, renal, metabolic, neurological...)
- Tobacco consumption > 5 cigarettes/days
- Alcohol consumption > 3 units/days (1 unit=1 drink)
- Subject under trusteeship or guardianship
- Subject unaffiliated with the social security
- Person deprived of their liberty, adult protected by laws, person hospitalized
- Ongoing participation in another clinical research study
- Subject non-cooperative or respectful of obligations inherent in the participation in the study
Trial locations and contacts
1 site in 1 country.
France1 site
Laboratoire EFCR - Functional Cardio-respiratory Exploration Laboratory
La Tronche, Isère, 38700
About this study
Official title: Cardiovascular and Metabolic Physiological Adaptations to Intermittent Hypoxia. Physiological Aspects and Expression of Receptors and Cellular Mediators
The purpose of this study is to compare cardiovascular physiological adaptation to intermittent hypoxia (IH) of nonobese healthy subjects. The exposure will be two periods of two weeks (IH versus exposure "placebo hypoxia"). The investigators will use pharmacological tools, peripheral vasodilator (amlodipine) or specific blocker of angiotensin receptor (valsartan) versus the taking of a placebo. The allocation of the tool and the exhibition will be randomized (HI / placebo, valsartan / amlodipine). The outcome measures evaluated concern the cardiovascular system, systemic inflammation and tissular and glucose metabolism.
The investigators assume an increase in arterial resistance during the intermittent hypoxia compared to the control group, these being dependent on sympathetic tone.
Read more
The investigators hypothesize that the metabolic alterations that will be observed after experimental simulation (IH and fragmentation of sleep for 15 consecutive nights) will be less severe in the valsartan group than in the amlodipine group in comparison with the placebo group.
A serum bank and a gene bank will be performed for the requirements of subsequent studies if necessary.
Read the detailed description
There are many physiological situations in which the organism is exposed to hypoxia, such as exercise and altitude. In addition some pathological situations also involve hypoxia, such as obesity, heart failure, respiratory failure and sleep apnea syndrome.
Hypoxia associated with altitude is frequently marked by the presence of sleep during periodic breathing induces a particular pattern of hypoxia called intermittent hypoxia. Also some subjects are "intolerant altitude" and develop specific pathologies at high altitude (acute mountain evil, pulmonary edema ...).
We recently demonstrated that subjects tolerate the altitude had just intermittent hypoxia while they were sleeping during the simulated altitude. The protective role of intermittent hypoxia in the mechanisms of occurrence of intolerance to altitude remains to be understood more precisely. In fact those who were intolerant to altitude has no periodic breathing and therefore intermittent hypoxia during the oxygen-deficient atmosphere.
Conversely, the sleep apnea syndrome (SAS) also characterized by a HI. It is produced by repeated episodes of airway obstruction during sleep, producing a sequence: respiratory effort, hypoxia / re-oxygenation and sleep interruption.
The HI is associated with both a well established cardiovascular morbidity but also to cardioprotection. This relates to cardiovascular morbidity rise in blood pressure can certainly promote the development after many years of hypertension. On the other hand the presence of sleep apnea syndrome is advanced as a factor favoring the coronary collateral circulation and therefore will bring a cardioprotective effect for patients.
Understanding the mechanisms of physiological adaptations to intermittent hypoxia by passing a deleterious evolution of a protective HI is therefore critical.
Exposure to altitude or OSAS induces the activation of intermediary mechanisms such as sympathetic activation, altered vascular reactivity, systemic inflammation and low-grade oxidative stress. The direct involvement of these mechanisms is dependent mainly intermediate of intermittent hypoxia. The shift in equilibrium between activator and inhibitor factors will evolve either to a protective mode (adaptation to altitude) or pathologic (cardiovascular complication of OSA).
Sympathetic activation has been demonstrated in patients with OSAS, reversible with effective treatment. The importance of cardiovascular sympathetic activation in elevating blood pressure by intermittent hypoxia is shown in animal models of HI. We also found an increase in sympathetic activation in our reversible model of HI in healthy subjects.
The elevation of that sympathetic activity is assumed to be multifactorial. An increase in tone but also a central potentiation thereof by an increase in peripheral chemoreflex sensitivity (sensitive to hypoxia) and against a lack of regulation by the arterial baroreflex.
Moreover angiotensin system modulates the central sympathetic tone and peripheral chemoreflex sensitivity. These actions are complementary in a signaling pathway of particular interest in exposure to intermittent hypoxia.
- Conditions
- Hypoxia, Sleep Apnea, Obstructive Sleep Apnea
- Being tested
- Placebo, Valsartan, Amlodipine
- Keywords
- Hypoxia, Sleep apnea, Valsartan, Amlodipine, Healthy subjects, Randomized, Cross-over, International, Sympathetic nervous system
- Medical subject headings
- Hypoxia, Sleep Apnea Syndromes, Sleep Apnea, Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Also called Placebo Valsartan
The subjects receive 1 oral pill of placebo each morning during the second week of the two periods, so 14 pills in all.
PlaceboDrug
Also called Placebo Almodipine
The subjects receive 1 oral pill of placebo each morning during the second week of the two periods, so 14 pills in all.
ValsartanDrug
Also called Tareg
The subjects receive 1 oral pill of Valsartan each morning during the second week of the two periods, so 14 pills in all. 1 pill equal 40 mg.
AmlodipineDrug
Also called Effective Amlodipine
The subjects receive 1 oral pill of Amlodipine each morning during the second week of the two periods, so 14 pills in all. 1 pill equal 6,944 mg of amlodipine besilate with 5 mg of amlodipine.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Real hypoxia and ¨Placebo | Placebo comparator | This arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the real hypoxia and the placebo during the first two weeks and, after the wash-out, receive the treatment of the arm 2. Receives: Drug: Placebo |
| Arm 2: Hypoxia placebo and Placebo | Placebo comparator | This arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the hypoxia placebo and the placebo during the first two weeks and, after the wash-out, receive the treatment of the arm 1. Receives: Drug: Placebo |
| Arm 3: Hypoxia and Valsartan | Active comparator | This arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the real hypoxia and the Valsartan during the first two weeks and, after the wash-out, receive the treatment of the arm 4. Receives: Drug: Valsartan |
| Arm 4: Hypoxia and Amlodipine | Active comparator | This arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the real hypoxia and the amlodipine during the first two weeks and, after the wash-out, receive the treatment of the arm 3. Receives: Drug: Amlodipine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in sympathetic activity
The sympathetic activity will be directly measured by microneurography of the peroneal nerve
Measured: Day 1 and at Day 14
Secondary outcomes (7)
Measure of adrenergic, inflammatory and metabolic markers in adipose tissues by chronic intermittent hypoxia versus placebo in healthy nonobese subjects.
The adrenergic receptors will be evaluated by immuno histochemistry appearance and by measuring mRNA levels of alpha and beta and AT1 and AT2 receptors by RT-PCR on total RNA extracted from the subcutaneous adipose tissue.
Insulin sensitivity test would be performed on adipose tissues.
Measured: Day 14
Measure variations in parameters of inflammation in adipose tissue by chronic intermittent hypoxia versus placebo in healthy nonobese subjects.
The inflammation will be assessed by measuring mRNA levels of proinflammatory cytokines and anti-inflammatory (IL-1, IL-6, IL-4, IL-10, IL-12, RANTES, TNF, leptin, adiponectin, CD68 (macrophage inflammation)) by RT-PCR on total RNA extracted (Mirvana, Ambion) from the subcutaneous adipose tissue.
Measured: Day 14
Measure of metabolic aspects of the OGTT test.
Measure of glucose intolerance and insulin sensitivity inducing by intermittent hypoxia by multisamples OGTT test.
Measured: Day 14
Measure the activation of systemic inflammation by chronic HI versus placebo in healthy nonobese subjects. The systemic inflammation will be assessed in non-stress and during the OGTT.
- Non-stress: by measuring the cytokines pro-and anti-inflammatory (IL-1, IL-6, IL-4, IL-10, IL-12, RANTES, TNF, leptin, adiponectin, CD68).
- OGTT: Kinetics concentrations of C-reactive protein, TNF-α, IL6, IL8, IL1-ß, CCL2/MCP-1, PAI-1, IL-1 Ra, IL-10.
Measured: Day 14
Assessing markers implicated in the pathophysiology of chronic metabolic diseases after HI versus placebo in healthy nonobese subjects during OGTT.
- Psychology:Hunger, appetite and food preference by validated questionnaires.
- Behavior:Calorie intake, food choices, energy expenditure.
- Physiology:
- Metabolism rest:Indirect calorimetry.
- Carbohydrate metabolism:Glucose tolerance, sensitivity to insulin, insulin secretion, time profiles of several proteins.
- Neuroendocrine control of appetite:Temporal Patterns of hormones.
- Lipid profiles:Temporal Patterns of FFA, concentrations of triglycerides and cholesterol.
- Autonomic nervous system activity:Cardiac inter-beat intervals, urine sample, time profiles of catecholamines.
Measured: Day 14
Change in vascular responsivness
Some others vascular beds will be explored skin, eyes before and after intermittent hypoxia.Use o f a laser doppler cutaneous, choroidal and ophthalmic arteries.
Measured: At day 1 and Day 14
Change in Sympathetic and vascular determinant of Blood pressure
Heart rate variability and vascular flow and arterial pressure. Heart rate variability will be measure from 24h ECG recording.The vascular flow will be measured by Doppler waveform of the popliteal artery. The blood pressure will be measured by an ambulatory blood pressure monitoring.
Measured: Day 1 and Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2014 (estimated)
- Study start7 Aug 2013
- Primary completion17 Jul 2014
- Study completion16 Mar 2017
Why it stopped: budget constraints
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (32)Papers the sponsor has linked to this study.
- Other trials for HypoxiaStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Renaud RT Tamisier, PhD, Principal investigator, University Hospital of Genoble
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02058823
- Sponsor's protocol ID
- 2011-32
- Other IDs
- P-2011-32-HI2
- Acronym
- IH2
- Status last verified
- Dec 2018
- First submitted
- 18 Apr 2012
- Last updated
- 31 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Steiner S, Schueller PO, Schulze V, Strauer BE. Occurrence of coronary collateral vessels in patients with sleep apnea and total coronary occlusion. Chest. 2010 Mar;137(3):516-20. doi: 10.1378/chest.09-1136. Epub 2009 Oct 26.
PubMed 19858231Lavie L. Obstructive sleep apnoea syndrome--an oxidative stress disorder. Sleep Med Rev. 2003 Feb;7(1):35-51. doi: 10.1053/smrv.2002.0261.
PubMed 12586529Shamsuzzaman AS, Gersh BJ, Somers VK. Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA. 2003 Oct 8;290(14):1906-14. doi: 10.1001/jama.290.14.1906.
PubMed 14532320Carlson JT, Hedner J, Elam M, Ejnell H, Sellgren J, Wallin BG. Augmented resting sympathetic activity in awake patients with obstructive sleep apnea. Chest. 1993 Jun;103(6):1763-8. doi: 10.1378/chest.103.6.1763.
PubMed 8404098Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest. 1995 Oct;96(4):1897-904. doi: 10.1172/JCI118235.
PubMed 7560081Hedner J, Darpo B, Ejnell H, Carlson J, Caidahl K. Reduction in sympathetic activity after long-term CPAP treatment in sleep apnoea: cardiovascular implications. Eur Respir J. 1995 Feb;8(2):222-9. doi: 10.1183/09031936.95.08020222.
PubMed 7758555Fletcher EC, Lesske J, Culman J, Miller CC, Unger T. Sympathetic denervation blocks blood pressure elevation in episodic hypoxia. Hypertension. 1992 Nov;20(5):612-9. doi: 10.1161/01.hyp.20.5.612.
PubMed 1428112Tamisier R, Pepin JL, Remy J, Baguet JP, Taylor JA, Weiss JW, Levy P. 14 nights of intermittent hypoxia elevate daytime blood pressure and sympathetic activity in healthy humans. Eur Respir J. 2011 Jan;37(1):119-28. doi: 10.1183/09031936.00204209. Epub 2010 Jun 4.
PubMed 20525723Narkiewicz K, van de Borne PJ, Montano N, Dyken ME, Phillips BG, Somers VK. Contribution of tonic chemoreflex activation to sympathetic activity and blood pressure in patients with obstructive sleep apnea. Circulation. 1998 Mar 17;97(10):943-5. doi: 10.1161/01.cir.97.10.943.
PubMed 9529260Carlson JT, Hedner JA, Sellgren J, Elam M, Wallin BG. Depressed baroreflex sensitivity in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 1996 Nov;154(5):1490-6. doi: 10.1164/ajrccm.154.5.8912770.
PubMed 8912770Punjabi NM, Beamer BA. Alterations in Glucose Disposal in Sleep-disordered Breathing. Am J Respir Crit Care Med. 2009 Feb 1;179(3):235-40. doi: 10.1164/rccm.200809-1392OC. Epub 2008 Nov 14.
PubMed 19011148Spiegel K, Tasali E, Leproult R, Van Cauter E. Effects of poor and short sleep on glucose metabolism and obesity risk. Nat Rev Endocrinol. 2009 May;5(5):253-61. doi: 10.1038/nrendo.2009.23.
PubMed 19444258Larsen JJ, Hansen JM, Olsen NV, Galbo H, Dela F. The effect of altitude hypoxia on glucose homeostasis in men. J Physiol. 1997 Oct 1;504 ( Pt 1)(Pt 1):241-9. doi: 10.1111/j.1469-7793.1997.241bf.x.
PubMed 9350634Braun B, Rock PB, Zamudio S, Wolfel GE, Mazzeo RS, Muza SR, Fulco CS, Moore LG, Butterfield GE. Women at altitude: short-term exposure to hypoxia and/or alpha(1)-adrenergic blockade reduces insulin sensitivity. J Appl Physiol (1985). 2001 Aug;91(2):623-31. doi: 10.1152/jappl.2001.91.2.623.
PubMed 11457773Spiegel K, Knutson K, Leproult R, Tasali E, Van Cauter E. Sleep loss: a novel risk factor for insulin resistance and Type 2 diabetes. J Appl Physiol (1985). 2005 Nov;99(5):2008-19. doi: 10.1152/japplphysiol.00660.2005.
PubMed 16227462
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiovascular and Metabolic Physiological Adaptations to Intermittent Hypoxia. Physiological Aspects and Expression of Receptors and Cellular Mediators
- ClinicalTrials.gov ID
- NCT02058823
- Acronym / sponsor ID
- IH2 / 2011-32
- Conditions
- Hypoxia, Sleep Apnea, Obstructive Sleep Apnea
- Keywords
- Hypoxia, Sleep apnea, Valsartan, Amlodipine, Healthy subjects, Randomized, Cross-over, International
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: budget constraints
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France
- Study start
- 7 Aug 2013 (actual)
- Primary completion
- 17 Jul 2014 (actual)
- Study completion
- 16 Mar 2017 (actual)
- First posted
- 10 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to compare cardiovascular physiological adaptation to intermittent hypoxia (IH) of nonobese healthy subjects. The exposure will be two periods of two weeks (IH versus exposure "placebo hypoxia"). The investigators will use pharmacological tools, peripheral vasodilator (amlodipine) or specific blocker of angiotensin receptor (valsartan) versus the taking of a placebo. The allocation of the tool and the exhibition will be randomized (HI / placebo, valsartan / amlodipine). The outcome measures evaluated concern the cardiovascular system, systemic inflammation and tissular and glucose metabolism.
The investigators assume an increase in arterial resistance during the intermittent hypoxia compared to the control group, these being dependent on sympathetic tone.
The investigators hypothesize that the metabolic alterations that will be observed after experimental simulation (IH and fragmentation of sleep for 15 consecutive nights) will be less severe in the valsartan group than in the amlodipine group in comparison with the placebo group.
A serum bank and a gene bank will be performed for the requirements of subsequent studies if necessary.
Detailed description
There are many physiological situations in which the organism is exposed to hypoxia, such as exercise and altitude. In addition some pathological situations also involve hypoxia, such as obesity, heart failure, respiratory failure and sleep apnea syndrome.
Hypoxia associated with altitude is frequently marked by the presence of sleep during periodic breathing induces a particular pattern of hypoxia called intermittent hypoxia. Also some subjects are "intolerant altitude" and develop specific pathologies at high altitude (acute mountain evil, pulmonary edema ...).
We recently demonstrated that subjects tolerate the altitude had just intermittent hypoxia while they were sleeping during the simulated altitude. The protective role of intermittent hypoxia in the mechanisms of occurrence of intolerance to altitude remains to be understood more precisely. In fact those who were intolerant to altitude has no periodic breathing and therefore intermittent hypoxia during the oxygen-deficient atmosphere.
Conversely, the sleep apnea syndrome (SAS) also characterized by a HI. It is produced by repeated episodes of airway obstruction during sleep, producing a sequence: respiratory effort, hypoxia / re-oxygenation and sleep interruption.
The HI is associated with both a well established cardiovascular morbidity but also to cardioprotection. This relates to cardiovascular morbidity rise in blood pressure can certainly promote the development after many years of hypertension. On the other hand the presence of sleep apnea syndrome is advanced as a factor favoring the coronary collateral circulation and therefore will bring a cardioprotective effect for patients.
Understanding the mechanisms of physiological adaptations to intermittent hypoxia by passing a deleterious evolution of a protective HI is therefore critical.
Exposure to altitude or OSAS induces the activation of intermediary mechanisms such as sympathetic activation, altered vascular reactivity, systemic inflammation and low-grade oxidative stress. The direct involvement of these mechanisms is dependent mainly intermediate of intermittent hypoxia. The shift in equilibrium between activator and inhibitor factors will evolve either to a protective mode (adaptation to altitude) or pathologic (cardiovascular complication of OSA).
Sympathetic activation has been demonstrated in patients with OSAS, reversible with effective treatment. The importance of cardiovascular sympathetic activation in elevating blood pressure by intermittent hypoxia is shown in animal models of HI. We also found an increase in sympathetic activation in our reversible model of HI in healthy subjects.
The elevation of that sympathetic activity is assumed to be multifactorial. An increase in tone but also a central potentiation thereof by an increase in peripheral chemoreflex sensitivity (sensitive to hypoxia) and against a lack of regulation by the arterial baroreflex.
Moreover angiotensin system modulates the central sympathetic tone and peripheral chemoreflex sensitivity. These actions are complementary in a signaling pathway of particular interest in exposure to intermittent hypoxia.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Real hypoxia and ¨Placebo | Placebo comparator | Drug: PlaceboThis arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the real hypoxia and the placebo during the first two weeks and, after the wash-out, receive the treatment of the arm 2. |
| Arm 2: Hypoxia placebo and Placebo | Placebo comparator | Drug: PlaceboThis arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the hypoxia placebo and the placebo during the first two weeks and, after the wash-out, receive the treatment of the arm 1. |
| Arm 3: Hypoxia and Valsartan | Active comparator | Drug: ValsartanThis arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the real hypoxia and the Valsartan during the first two weeks and, after the wash-out, receive the treatment of the arm 4. |
| Arm 4: Hypoxia and Amlodipine | Active comparator | Drug: AmlodipineThis arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the real hypoxia and the amlodipine during the first two weeks and, after the wash-out, receive the treatment of the arm 3. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Healthy subject
- Subject aged of 18 years-old at least
- Diagnostic AHI<15/h and <5% of total sleep time spent with a SaO2<90%
- Free and informed consent signed
- Subject covered by social security
Key exclusion criteria (8 listed)
- Subject with a medical pathology (respiratory, cardiovascular, renal, metabolic, neurological...)
- Tobacco consumption > 5 cigarettes/days
- Alcohol consumption > 3 units/days (1 unit=1 drink)
- Subject under trusteeship or guardianship
- Subject unaffiliated with the social security
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboAlso: Placebo ValsartanThe subjects receive 1 oral pill of placebo each morning during the second week of the two periods, so 14 pills in all. | Drug | Arm 1: Real hypoxia and ¨Placebo |
| PlaceboAlso: Placebo AlmodipineThe subjects receive 1 oral pill of placebo each morning during the second week of the two periods, so 14 pills in all. | Drug | Arm 2: Hypoxia placebo and Placebo |
| ValsartanAlso: TaregThe subjects receive 1 oral pill of Valsartan each morning during the second week of the two periods, so 14 pills in all. 1 pill equal 40 mg. | Drug | Arm 3: Hypoxia and Valsartan |
| AmlodipineAlso: Effective AmlodipineThe subjects receive 1 oral pill of Amlodipine each morning during the second week of the two periods, so 14 pills in all. 1 pill equal 6,944 mg of amlodipine besilate with 5 mg of amlodipine. | Drug | Arm 4: Hypoxia and Amlodipine |
Primary outcome
Change in sympathetic activity
Time frame: Day 1 and at Day 14
The sympathetic activity will be directly measured by microneurography of the peroneal nerve
7 secondary outcomes
Measure of adrenergic, inflammatory and metabolic markers in adipose tissues by chronic intermittent hypoxia versus placebo in healthy nonobese subjects.
Time frame: Day 14
Measure variations in parameters of inflammation in adipose tissue by chronic intermittent hypoxia versus placebo in healthy nonobese subjects.
Time frame: Day 14
Measure of metabolic aspects of the OGTT test.
Time frame: Day 14
Measure the activation of systemic inflammation by chronic HI versus placebo in healthy nonobese subjects. The systemic inflammation will be assessed in non-stress and during the OGTT.
Time frame: Day 14
Assessing markers implicated in the pathophysiology of chronic metabolic diseases after HI versus placebo in healthy nonobese subjects during OGTT.
Time frame: Day 14
Change in vascular responsivness
Time frame: At day 1 and Day 14
Change in Sympathetic and vascular determinant of Blood pressure
Time frame: Day 1 and Day 14
Results and safety
The study was stopped early (reason given: budget constraints). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2018.
- Background: PubMed 19858231Steiner S, Schueller PO, Schulze V, Strauer BE. Occurrence of coronary collateral vessels in patients with sleep apnea and total coronary occlusion. Chest. 2010 Mar;137(3):516-20. doi: 10.1378/chest.09-1136. Epub 2009 Oct 26.
- Background: PubMed 12586529Lavie L. Obstructive sleep apnoea syndrome--an oxidative stress disorder. Sleep Med Rev. 2003 Feb;7(1):35-51. doi: 10.1053/smrv.2002.0261.
- Background: PubMed 14532320Shamsuzzaman AS, Gersh BJ, Somers VK. Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA. 2003 Oct 8;290(14):1906-14. doi: 10.1001/jama.290.14.1906.
- Background: PubMed 8404098Carlson JT, Hedner J, Elam M, Ejnell H, Sellgren J, Wallin BG. Augmented resting sympathetic activity in awake patients with obstructive sleep apnea. Chest. 1993 Jun;103(6):1763-8. doi: 10.1378/chest.103.6.1763.
- Background: PubMed 7560081Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest. 1995 Oct;96(4):1897-904. doi: 10.1172/JCI118235.
- Background: PubMed 7758555Hedner J, Darpo B, Ejnell H, Carlson J, Caidahl K. Reduction in sympathetic activity after long-term CPAP treatment in sleep apnoea: cardiovascular implications. Eur Respir J. 1995 Feb;8(2):222-9. doi: 10.1183/09031936.95.08020222.
- Background: PubMed 1428112Fletcher EC, Lesske J, Culman J, Miller CC, Unger T. Sympathetic denervation blocks blood pressure elevation in episodic hypoxia. Hypertension. 1992 Nov;20(5):612-9. doi: 10.1161/01.hyp.20.5.612.
- Background: PubMed 20525723Tamisier R, Pepin JL, Remy J, Baguet JP, Taylor JA, Weiss JW, Levy P. 14 nights of intermittent hypoxia elevate daytime blood pressure and sympathetic activity in healthy humans. Eur Respir J. 2011 Jan;37(1):119-28. doi: 10.1183/09031936.00204209. Epub 2010 Jun 4.
- Background: PubMed 9529260Narkiewicz K, van de Borne PJ, Montano N, Dyken ME, Phillips BG, Somers VK. Contribution of tonic chemoreflex activation to sympathetic activity and blood pressure in patients with obstructive sleep apnea. Circulation. 1998 Mar 17;97(10):943-5. doi: 10.1161/01.cir.97.10.943.
- Background: PubMed 8912770Carlson JT, Hedner JA, Sellgren J, Elam M, Wallin BG. Depressed baroreflex sensitivity in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 1996 Nov;154(5):1490-6. doi: 10.1164/ajrccm.154.5.8912770.
- Background: PubMed 19011148Punjabi NM, Beamer BA. Alterations in Glucose Disposal in Sleep-disordered Breathing. Am J Respir Crit Care Med. 2009 Feb 1;179(3):235-40. doi: 10.1164/rccm.200809-1392OC. Epub 2008 Nov 14.
- Background: PubMed 19444258Spiegel K, Tasali E, Leproult R, Van Cauter E. Effects of poor and short sleep on glucose metabolism and obesity risk. Nat Rev Endocrinol. 2009 May;5(5):253-61. doi: 10.1038/nrendo.2009.23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Renaud RT Tamisier, PhD principal investigator
University Hospital of Genoble
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Valsartan and Amlodipine in people with Hypoxia and Sleep Apnea, run by University Hospital, Grenoble at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: budget constraints). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in sympathetic activity (time frame: Day 1 and at Day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02058823, which also lists 32 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2018.