To investigate the difference in response between single and double vital capacity 35% CO2/65% O2 in terms of the occurrence of PA*s in healthy subjects as measured with the Panic Symptoms List-IV (PSL-IV) and VAS subjective anxiety and fear.
ID
Source
Brief title
Condition
- Anxiety disorders and symptoms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Panic attacks will be assessed by the Panic Symptoms List-IV (PSL-IV) and VAS
subjective anxiety and fear.
Secondary outcome
* explore whether the occurrence of PA*s on a single vital capacity inhalation
35% CO2/65% O2 predicts occurrence of PA*s on a double vital capacity
inhalation 35% CO2/65% O2.
* explore the temporal stability of the occurrence of 35% CO2/65% O2-induced
PA*s in subjects who develop PA*s on a single vital capacity inhalation and
subsequently receive a double vital capacity inhalation.
* explore the effects of single and double breath 35% CO2/65% O2 on heart rate,
blood pressure, respiratory rate.
* explore differences in sensitivity to 35% CO2/65% O2 between male and female
subjects.
Background summary
CO2 inhalation to induce panic has undergone both technical innovation and
relatively extensive validation since the 1980*s.
Healthy volunteers display a concentration dependent sensitivity to inhaled CO2
while panic disorder (PD) patients consistently display the highest sensitivity
to CO2, followed by first degree relatives of PD patients and healthy
volunteers. In addition, registered anxiolytic drugs administered in clinically
effective therapeutic doses generally have been demonstrated to reduce
sensitivity CO2 in healthy volunteers and patients over time. Furthermore, the
panic response to acutely inhaled CO2 remains stable and reproducible over
time, tolerance does not occur after repeated administration and CO2-related
carry-over effects are non-existent. Also, CO2 induces robust fear-like
behaviour in preclinical models and demonstrates respiratory and cardiovascular
effects that correspond to those in humans. Acute CO2 inhalation therefore
represents a validated, translational fear challenge using a physiological
agent which allows real-time assessment of PA*s in an experimental setting and
has the potential to demonstrate panicolytic effects of novel central nervous
system (CNS) active compounds in humans.
To the best of our knowledge no study has been previously published that
compares single and double vital capacity 35% CO2 inhalation in a single study.
Therefore, we aim to investigate the panicogenic effects of a single vs. a
double vital capacity method 35% CO2 in healthy volunteers. We hypothesize that
35% CO2 double vital capacity inhalation is associated with a higher percentage
of subjects experiencing a panic attack compared to single vital capacity
inhalation.
Study objective
To investigate the difference in response between single and double vital
capacity 35% CO2/65% O2 in terms of the occurrence of PA*s in healthy subjects
as measured with the Panic Symptoms List-IV (PSL-IV) and VAS subjective anxiety
and fear.
Study design
A randomized, two-way cross-over validation trial to establish the occurrence
of PA*s with single and double breath 35% CO2/65% O2 vital capacity inhalation
in healthy volunteers.
Study burden and risks
The acute inhalation of CO2 has been developed, validated and technically
innovated over the past years as a reliable challenge model to induce an acute
panic reaction that adequately resembles PAs. CO2 and O2 are harmless
physiological substances that are inhaled according to a standardized challenge
protocol that has been developed by Maastricht University. Numerous studies in
several hundred healthy volunteers and patients suffering from panic disorder,
social anxiety disorder, post-traumatic stress disorder and major depressive
disorder have been conducted according to this protocol over the past 30 years.
In the majority of these studies, a mixture of 35% CO2/65% O2 had been
administered as either single or double vital capacity inhalation. In all
performed studies neither acute nor chronic adverse events have been reported.
Also, no serious adverse events have occurred. To guarantee identical
safeguards for the current study, the same absolute and relative
contra-indications will be maintained and are incorporated into the in- and
exclusion criteria of the protocol.
Maastricht Instruments in collaboration with Maastricht University has recently
developed the CO2 tolerance tester (CTT). The CTT is a research instrument that
safely and reliably induces PA*s by the protocolized administration of inhaled
35% CO2. In addition, the CTT simultaneously measures physiological changes
associated with CO2-induced ANS activation such has heart rate and blood
pressure. In contrast to previous experimental CO2 set ups, the CTT yields
integrated real time information on ANS panic-related parameters following
acute CO2 inhalation which can be readily combined with subjective assessments
such as fear intensity. The CTT is particularly relevant to research in the
field fear-related psychiatric disorders and is a potentially useful tool in
CNS drug development with novel anxiolytic compounds.
Zernikedreef 8
Leiden 2333CL
NL
Zernikedreef 8
Leiden 2333CL
NL
Listed location countries
Age
Inclusion criteria
1. Informed consent in writing.
2. Healthy male or female aged between 18 and 55 years (inclusive) at screening.
3. BMI of 18-32 kg/m2 (inclusive).
4. Non-smoker for at least 3 months.
5. Ability to communicate adequately with the Investigator in the Dutch language and is willing to comply with the study restrictions.
Exclusion criteria
1. Current or past history of any psychiatric disorder as classified according to DSM-IV or DSM 5.
2. Current or past history of alcohol or any substance abuse or dependence disorder within the past 12 months.
3. Presence of panic disorder as classified by DSM-IV and diagnosed by a psychiatrist or classified by the module Panic Disorder (E) of the MINI International Neuropsychiatric Interview during screening.
4. Subject drinks, on average, more than 8 cups of tea/coffee/cocoa/cola/caffeinated beverages (e.g., energy drink) per day.
5. Subject has a clinically significant acute illness within 7 days prior to the CO2 challenge.
6. Systolic blood pressure (SBP) greater than 140 or less than 90 mm Hg, and diastolic blood pressure (DBP) greater than 90 or less than 50 mm Hg
7. Clinically significant ECG abnormalities.
8. Clinically significant abnormality of the lungs (e.g. COPD, asthma, lung fibrosis) and hematologic diseases concerning hemoglobin (e.g. thalassemia and sickle cell disease).
9. Important cardiovascular history, or suspicion of infarct, cardiomyopathy, cardiac failure, TIA, angina pectoris, cardiac arrhythmias, CVA.
10. Personal or familial history of cerebral aneurysm.
11. Pregnancy as demonstrated by urine pregnancy test during screening or at each study day.
12. Use of any psychotropic drugs.
13. Have a urine drug screen detecting illicit drug of abuse (morphine, benzodiazepines, cocaine, amphetamine, THC) or a positive alcohol breath test at screening of elke studiedag
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL61306.056.17 |
| OMON | NL-OMON26851 |