Sleep DisorderPhase 1NCT06512155
Improving Perioperative Sleep Disorders
A Phase 1 study testing Pregabalin and Zolpidem in people with Sleep Disorder, run by Mengchang Yang at 1 site in China.
Trial summary
In today's day of increasing surgical volume, perioperative sleep disorders are an issue that cannot be ignored. They are an important component of perioperative brain protection. Physiologically and psychologically, sleep disorders cause serious damage to patients. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Sleep Disorder
- What is being tested?
- Pregabalin and Zolpidem
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 215 participants
- Where
- 1 siteChina
- Study dates
- 2 Jul 2024to 26 Dec 2024
- Phase
- Phase 1
- 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 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 18 years old ≤ Age ≤ 65 years old, gender unlimited.
- ASA level I-II.
- Plan to undergo elective total knee arthroplasty, total hip arthroplasty, and spinal vertebral body surgery.
Who cannot join
- Patients with preoperative sleep problems.
- Patients refuse to participate in the study.
- The patient has any allergies or contraindications to the drugs used in the study.
- The patient has a history of long-term use of medications such as pregabalin or gabapentin.
- The patient has a history of long-term use of any painkillers or sleeping pills.
- The patient has cognitive impairment and is unable to conduct visits and communication.
- The patient has a history of renal dysfunction or any other serious organ dysfunction.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Pregabalin on Perioperative Sleep Quality in Orthopedic Surgery Patients: a Prospective, Randomized, Controlled Study
In today's day of increasing surgical volume, perioperative sleep disorders are an issue that cannot be ignored. They are an important component of perioperative brain protection. Physiologically and psychologically, sleep disorders cause serious damage to patients. The application of pregabalin aims to improve the sleep quality of hand surgery patients, and its anti anxiety effect can also alleviate preoperative anxiety. At the same time, its analgesic mechanism is different from that of opioid drugs, which is also conducive to reducing the use of opioid drugs. Therefore, we propose the following hypothesis: for orthopedic patients with high incidence of postoperative pain and sleep disorders, the use of pregabalin will improve the perioperative sleep quality of such patients.To test the above hypothesis, our research group plans to conduct this prospective, randomized, positive control study.
Read the detailed description
Perioperative sleep disorders mainly refer to the syndrome in which patients undergoing surgery experience disrupted sleep wake rhythms before and/or after surgery, leading to abnormal sleep quality or behavior during sleep. Clinical manifestations include fragmented sleep, easy awakening at night, difficulty falling asleep, insufficient sleep time, early bedtime, or disrupted sleep rhythm at least one day before or after surgery. The latest meta-analysis study indicates that the incidence of preoperative sleep disorders in surgical patients is as high as 60%. After surgery, about 60-70% of patients will have postoperative sleep disorder (PSD), and even 23% of patients will have sleep disorder until the fourth day after surgery. Among various surgeries, orthopedic surgery has a high incidence of PSD due to its long operation time and wide surgical range. In the study by Duan G and colleagues, the PSD incidence rate of spinal orthopedic surgery in orthopedics was 35.4%, and the PSD incidence rate of limb surgery was 27%.
Sleep disorders may lead to a range of complications, including cognitive impairment, delayed postoperative recovery, acute pain, and cardiovascular accidents. In the hospital environment, factors that lead to poor sleep include pain, anxiety, noise, interference from hospital staff, continuous ambient lighting, and uncomfortable beds; After completing the surgery, factors such as the size of the surgery, the use of opioid drugs, inflammatory mediators, the release of various hormones, and pain contribute to a high incidence of sleep disorders, with pain being the most common cause, and there is an interactive relationship between postoperative sleep disorders and pain. It is worth noting that patients with poor preoperative sleep quality have a higher probability of developing sleep disorders after surgery. Therefore, it is necessary to comprehensively consider these factors and take corresponding preventive measures to reduce the incidence of perioperative sleep disorders.
According to the sleep care guidelines, for postoperative patients entering the ICU, maintaining a quiet and dim environment and reducing interruptions in nighttime care activities are recommended to improve sleep quality and efficiency. A meta-analysis shows that the use of earplugs and eye masks also helps promote sleep in ICU patients. However, it is evident that this method is not suitable for patients who are admitted to regular multi person wards after surgery. Although in a meta-analysis, there was insufficient evidence to suggest that drug therapy can improve the quality or quantity of sleep in patients with poor postoperative sleep. Even compared to placebo or no treatment, there is no established drug category or specific drug that is superior to placebo or no treatment [6]. However, drug therapy is still widely used for patients with perioperative sleep disorders due to its convenience, strong feasibility, and high patient acceptance.
In current clinical practice, the main drugs used to address perioperative sleep disorders are sleeping pills and painkillers. Specifically, sleeping pills are mainly divided into first generation, second generation, and third generation sedative hypnotic drugs. These drugs mainly exert extensive inhibition on the central nervous system, causing it to transition from an excited state to an inhibited state. However, their effect on improving sleep structure is not satisfactory, especially the second-generation drugs - benzodiazepines, which can change the usual sleep pattern, prolong shallow sleep, shorten the duration of REM sleep, and delay the appearance of the first REM sleep. This change, which is similar to the postoperative sleep structure, is more detrimental to the improvement of patients' sleep, therefore the effect is not satisfactory. As for painkillers, opioids are the most commonly used class in clinical practice. Even though they have strong analgesic effects, they have been found to dose dependently inhibit REM and SWS sleep in normal volunteers and animal experiments. In addition, in Cronin AJ et al.'s study, postoperative patients suffered from severe sleep disorders even when avoiding opioid use and pain was well controlled. Therefore, the improvement of sleep in perioperative patients cannot be limited to the use of the above two drugs.
Pregabalin is a gabapentin class drug that inhibits the influx of calcium ions into the presynaptic membrane of neurons and reduces the release of excitatory neurotransmitters (including glutamate, aspartic acid, substance P, calcitonin gene-related peptide, norepinephrine, serotonin, dopamine, etc.) by binding to the α 2 δ pressure group containing voltage-gated calcium channels. Its analgesic, anti anxiety, and anticonvulsant effects are widely used in various clinical diseases. Pregabalin has been approved for the treatment of neuropathic pain and partial seizures in the United States and Europe. It can also be used for fibromyalgia in the United States and for the treatment of generalized anxiety disorder in Europe. While treating patients with this type of chronic disease, its effect on improving sleep has been discovered. Studies have found that pregabalin exhibits significant sleep improvement effects from the initial stage of medication, and its therapeutic efficacy is maintained throughout the entire treatment phase. Similar sleep improvement effects to alprazolam have also been found in normal healthy individuals. The mechanism by which pregabalin improves sleep is still unclear, and it is speculated to be related to its ability to reduce excitatory neurotransmitters. Currently, there is no relevant research on the impact of pregabalin on sleep quality in perioperative patients.
- Conditions
- Sleep Disorder
- Being tested
- Pregabalin, Zolpidem
- Medical subject headings
- Sleep Wake Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PregabalinDrug
Also called Pregabalin Capsules (Lerika)
Start taking 75mg bid of pregabalin two days before surgery, and take 150mg bid of pregabalin from one day before surgery to three days after surgery
ZolpidemDrug
Also called Zolpidem Tartrate Tablets(Sinuosi)
Take zolpidem 10mg qn from two days before surgery to three days after surgery
| Study group | Role | What they receive |
|---|---|---|
| Pregabalin Group | Experimental | The Pregabalin group started taking Pregabalin 75mg bid two days before surgery and Pregabalin 150mg bid from the day before surgery to three days after surgery Receives: Drug: Pregabalin |
| Zolpidem Group | Experimental | Patients in the zolpidem group took zolpidem 10mg every night from two days before surgery to three days after surgery Receives: Drug: Zolpidem |
| Control group | No intervention | Control group patients do not take any additional medication that affects sleep |
What is being measured
The primary outcome is the main question the study is designed to answer.
Athens Insomnia Scale
The Athens Insomnia Scale has a minimum score of zero and a maximum score of 24. When the score is greater than or equal to 6, it indicates the presence of sleep disorders, and the higher the score, the more severe the sleep disorders.
Measured: From the second day of medication to five days after surgery
Secondary outcomes (8)
Pittsburgh Sleep Quality Index score
The total score range of the Pittsburgh Sleep Quality Index is 0-21 points. The higher the score, the worse the sleep quality. An index greater than or equal to 8 points is considered to have a sleep quality issue
Measured: On the 30th day after surgery
Hamilton Anxiety Scale (HAMA)
A total score of ≥ 29 on the Hamilton Anxiety Scale may indicate severe anxiety 21 points, there must be obvious anxiety; ≥ 14 points, there must be anxiety; Exceeding 7 points may indicate anxiety; If it is less than 7 points, there are no symptoms of anxiety.
Measured: Two days before surgery and five days after surgery
VAS score
Evaluate patient pain using VAS score five days after surgery
Measured: Five days after surgery
Perioperative opioid consumption
Perioperative opioid consumption, converted to morphine equivalent
Measured: Immediately after discharge
Postoperative hospitalization time
Postoperative hospitalization time
Measured: Immediately after discharge
The incidence of various adverse events
The incidence of various adverse events, including fatigue, drowsiness, dizziness, nausea and vomiting, blurred vision, and other psychological symptoms such as hallucinations, agitation, nightmares, depression, etc
Measured: Immediately after discharge
Patient satisfaction survey
The patient satisfaction survey during hospitalization is divided into four levels: very satisfied, relatively satisfied, relatively dissatisfied, and very dissatisfied.
Measured: Immediately after discharge
Hamilton Depression Scale(HAMD)
Hamilton Depression Scale total score<7: normal; A total score of 7-17 indicates possible depression; A total score of 17-24 points indicates the presence of depression; Total score>24: Severe depression。
Measured: Two days before surgery and five days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2024
- Study start2 Jul 2024
- Primary completion30 Nov 2024
- Study completion26 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sleep DisorderStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 215 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mengchang Yang
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Mengchang Yang, Sichuan Provincial People's Hospital
- Investigators
- Yang Mengchang, Doctor, Principal investigator, Sichuan Provincial People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06512155
- Sponsor's protocol ID
- Sleep disorders-1
- Status last verified
- Jul 2024
- First submitted
- 24 Jun 2024
- Last updated
- 30 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Pregabalin on Perioperative Sleep Quality in Orthopedic Surgery Patients: a Prospective, Randomized, Controlled Study
- ClinicalTrials.gov ID
- NCT06512155
- Acronym / sponsor ID
- Sleep disorders-1
- Conditions
- Sleep Disorder
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 215 participants (actual)
- Lead sponsor
- Mengchang YangUniversity, hospital or other
- Study start
- 2 Jul 2024 (actual)
- Primary completion
- 30 Nov 2024 (actual)
- Study completion
- 26 Dec 2024 (actual)
- First posted
- 22 Jul 2024 (actual)
- 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.
In today's day of increasing surgical volume, perioperative sleep disorders are an issue that cannot be ignored. They are an important component of perioperative brain protection. Physiologically and psychologically, sleep disorders cause serious damage to patients. The application of pregabalin aims to improve the sleep quality of hand surgery patients, and its anti anxiety effect can also alleviate preoperative anxiety. At the same time, its analgesic mechanism is different from that of opioid drugs, which is also conducive to reducing the use of opioid drugs. Therefore, we propose the following hypothesis: for orthopedic patients with high incidence of postoperative pain and sleep disorders, the use of pregabalin will improve the perioperative sleep quality of such patients.To test the above hypothesis, our research group plans to conduct this prospective, randomized, positive control study.
Detailed description
Perioperative sleep disorders mainly refer to the syndrome in which patients undergoing surgery experience disrupted sleep wake rhythms before and/or after surgery, leading to abnormal sleep quality or behavior during sleep. Clinical manifestations include fragmented sleep, easy awakening at night, difficulty falling asleep, insufficient sleep time, early bedtime, or disrupted sleep rhythm at least one day before or after surgery. The latest meta-analysis study indicates that the incidence of preoperative sleep disorders in surgical patients is as high as 60%. After surgery, about 60-70% of patients will have postoperative sleep disorder (PSD), and even 23% of patients will have sleep disorder until the fourth day after surgery. Among various surgeries, orthopedic surgery has a high incidence of PSD due to its long operation time and wide surgical range. In the study by Duan G and colleagues, the PSD incidence rate of spinal orthopedic surgery in orthopedics was 35.4%, and the PSD incidence rate of limb surgery was 27%.
Sleep disorders may lead to a range of complications, including cognitive impairment, delayed postoperative recovery, acute pain, and cardiovascular accidents. In the hospital environment, factors that lead to poor sleep include pain, anxiety, noise, interference from hospital staff, continuous ambient lighting, and uncomfortable beds; After completing the surgery, factors such as the size of the surgery, the use of opioid drugs, inflammatory mediators, the release of various hormones, and pain contribute to a high incidence of sleep disorders, with pain being the most common cause, and there is an interactive relationship between postoperative sleep disorders and pain. It is worth noting that patients with poor preoperative sleep quality have a higher probability of developing sleep disorders after surgery. Therefore, it is necessary to comprehensively consider these factors and take corresponding preventive measures to reduce the incidence of perioperative sleep disorders.
According to the sleep care guidelines, for postoperative patients entering the ICU, maintaining a quiet and dim environment and reducing interruptions in nighttime care activities are recommended to improve sleep quality and efficiency. A meta-analysis shows that the use of earplugs and eye masks also helps promote sleep in ICU patients. However, it is evident that this method is not suitable for patients who are admitted to regular multi person wards after surgery. Although in a meta-analysis, there was insufficient evidence to suggest that drug therapy can improve the quality or quantity of sleep in patients with poor postoperative sleep. Even compared to placebo or no treatment, there is no established drug category or specific drug that is superior to placebo or no treatment [6]. However, drug therapy is still widely used for patients with perioperative sleep disorders due to its convenience, strong feasibility, and high patient acceptance.
In current clinical practice, the main drugs used to address perioperative sleep disorders are sleeping pills and painkillers. Specifically, sleeping pills are mainly divided into first generation, second generation, and third generation sedative hypnotic drugs. These drugs mainly exert extensive inhibition on the central nervous system, causing it to transition from an excited state to an inhibited state. However, their effect on improving sleep structure is not satisfactory, especially the second-generation drugs - benzodiazepines, which can change the usual sleep pattern, prolong shallow sleep, shorten the duration of REM sleep, and delay the appearance of the first REM sleep. This change, which is similar to the postoperative sleep structure, is more detrimental to the improvement of patients' sleep, therefore the effect is not satisfactory. As for painkillers, opioids are the most commonly used class in clinical practice. Even though they have strong analgesic effects, they have been found to dose dependently inhibit REM and SWS sleep in normal volunteers and animal experiments. In addition, in Cronin AJ et al.'s study, postoperative patients suffered from severe sleep disorders even when avoiding opioid use and pain was well controlled. Therefore, the improvement of sleep in perioperative patients cannot be limited to the use of the above two drugs.
Pregabalin is a gabapentin class drug that inhibits the influx of calcium ions into the presynaptic membrane of neurons and reduces the release of excitatory neurotransmitters (including glutamate, aspartic acid, substance P, calcitonin gene-related peptide, norepinephrine, serotonin, dopamine, etc.) by binding to the α 2 δ pressure group containing voltage-gated calcium channels. Its analgesic, anti anxiety, and anticonvulsant effects are widely used in various clinical diseases. Pregabalin has been approved for the treatment of neuropathic pain and partial seizures in the United States and Europe. It can also be used for fibromyalgia in the United States and for the treatment of generalized anxiety disorder in Europe. While treating patients with this type of chronic disease, its effect on improving sleep has been discovered. Studies have found that pregabalin exhibits significant sleep improvement effects from the initial stage of medication, and its therapeutic efficacy is maintained throughout the entire treatment phase. Similar sleep improvement effects to alprazolam have also been found in normal healthy individuals. The mechanism by which pregabalin improves sleep is still unclear, and it is speculated to be related to its ability to reduce excitatory neurotransmitters. Currently, there is no relevant research on the impact of pregabalin on sleep quality in perioperative patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Pregabalin Group | Experimental | Drug: PregabalinThe Pregabalin group started taking Pregabalin 75mg bid two days before surgery and Pregabalin 150mg bid from the day before surgery to three days after surgery |
| Zolpidem Group | Experimental | Drug: ZolpidemPatients in the zolpidem group took zolpidem 10mg every night from two days before surgery to three days after surgery |
| Control group | No intervention | –Control group patients do not take any additional medication that affects sleep |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 18 years old ≤ Age ≤ 65 years old, gender unlimited.
- ASA level I-II.
- Plan to undergo elective total knee arthroplasty, total hip arthroplasty, and spinal vertebral body surgery.
Key exclusion criteria (7 listed)
- Patients with preoperative sleep problems.
- Patients refuse to participate in the study.
- The patient has any allergies or contraindications to the drugs used in the study.
- The patient has a history of long-term use of medications such as pregabalin or gabapentin.
- The patient has a history of long-term use of any painkillers or sleeping pills.
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 |
|---|---|---|
| PregabalinAlso: Pregabalin Capsules (Lerika)Start taking 75mg bid of pregabalin two days before surgery, and take 150mg bid of pregabalin from one day before surgery to three days after surgery | Drug | Pregabalin Group |
| ZolpidemAlso: Zolpidem Tartrate Tablets(Sinuosi)Take zolpidem 10mg qn from two days before surgery to three days after surgery | Drug | Zolpidem Group |
Primary outcome
Athens Insomnia Scale
Time frame: From the second day of medication to five days after surgery
The Athens Insomnia Scale has a minimum score of zero and a maximum score of 24. When the score is greater than or equal to 6, it indicates the presence of sleep disorders, and the higher the score, the more severe the sleep disorders.
8 secondary outcomes
Pittsburgh Sleep Quality Index score
Time frame: On the 30th day after surgery
Hamilton Anxiety Scale (HAMA)
Time frame: Two days before surgery and five days after surgery
VAS score
Time frame: Five days after surgery
Perioperative opioid consumption
Time frame: Immediately after discharge
Postoperative hospitalization time
Time frame: Immediately after discharge
The incidence of various adverse events
Time frame: Immediately after discharge
Patient satisfaction survey
Time frame: Immediately after discharge
Hamilton Depression Scale(HAMD)
Time frame: Two days before surgery and five days after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2024.
- Individual participant dataSharing planned: No
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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.
Yang Mengchang, Doctor principal investigator
Sichuan Provincial People's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pregabalin and Zolpidem in people with Sleep Disorder, run by Mengchang Yang at 1 site in China.
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 3 inclusion and 7 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: finished, as of the sponsor's last update on 30 Dec 2024. 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 China. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Athens Insomnia Scale (time frame: From the second day of medication to five days after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Dec 2024.