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Effectiveness of Acupuncture and Doxylamine/Pyridoxine for Moderate to Severe Nausea and Vomiting in Pregnancy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04401384
Recruitment Status : Completed
First Posted : May 26, 2020
Last Update Posted : April 4, 2022
Sponsor:
Collaborators:
Ningxia Hui Autonomous Region Hospital of TCM
Jiangxi Maternal and Child Health Hospital
Jixi Maternal and Child Health Hospital
Luoyang Hospital of TCM
Xuzhou Central Hospital
First Affiliated Hospital of Heilongjiang Chinese Medicine University
Shuangyashan Maternal and Child Health Hospital
Heilongjiang provincial hospital
Jiamusi Maternal and Child Health Hospital
Hegang Maternal and Child Health Hospital
Suihua Maternal and Child Health Hospital
Mudanjaing Maternal and Child Health Hospital
Affiliated Hospital of Jiamusi Medical University
Information provided by (Responsible Party):
Xiaoke Wu, Heilongjiang University of Chinese Medicine

Brief Summary:
Nausea and vomiting in pregnancy (NVP) is one of the most common symptoms of pregnancy affecting 50-85% of women during the first half of pregnancy. Maternal morbidity is common and includes psychological effects, financial burden, clinical complications from nutritional deficiencies, gastrointestinal trauma, and in rare cases, neurological damage. As the main means of alternative treatment, economical and easy to obtain; the clinical efficacy of acupuncture treatment of this disease has low level of evidence and needs to be reconfirmed. Doxylamine vitamin B6 sustained release tablets (Diclectin, combination of doxylamine succinate (10mg) and pyridoxine hydrochloride (10mg) are The American College of Obstetricians and Gynecologists recommends with Level A evidence the use of vitamin B6 in combination with doxylamine as first-line pharmacotherapy for treatment of NVP. The efficacy and safety of Diclectin has been confirmed in many years of research, but there is no evidence of high-level evidence-based medicine for the Chinese population. The purpose of this multicenter, randomized, double-blind, placebo-controlled trial was to investigate the efficacy and safety of acupuncture versus Diclectin in the treatment of NVP. We hypothesis that: (1)Sham acupuncture and Diclectin (Arm B) is more effective than sham acupuncture and placebo (Arm D); (2)Active acupuncture and placebo (Arm C) is more effective than sham acupuncture and placebo (Arm D); (3) There is no interaction (either synergistic or antagonistic effects) between the two interventions of active acupuncture and Diclectin in patients with NVP.

Condition or disease Intervention/treatment Phase
Nausea and Vomiting of Pregnancy Drug: Diclectin Drug: Diclectin placebo Device: Active acupuncture Device: Sham acupuncture Phase 3

Detailed Description:
Subjects will be randomized into one of the four treatment arms: A) active acupuncture (30 min /every day) + Diclectin (combination of doxylamine succinate (10 mg) and pyridoxine hydrochloride (10 mg) , 2-4 tablets/day); B) sham acupuncture (30 min /every day) + Diclectin (2-4 tablets/day); C) active acupuncture (30 min / every day) + Diclectin placebo (2-4 tablets/day); D) sham acupuncture (30 min /every day) + Diclectin placebo (2-4 tablets/day). Participants will receive active acupuncture or sham acupuncture treatment daily, 14 times in total, and receive Diclectin or placebo treatment every day (2 tablets at bedtime for the first two days, if the symptoms are unrelieved, add one tablet in the morning, if the symptoms are still unrelieved, add another one tablet at three o 'clock in the afternoon) for 2 consecutive weeks, 28-56 tablets in total. Daily measurement PUQE score, Visual analog scale (VAS), Adverse events and concomitant medications. Weekly visits will include global assessment of well being, adverse events and concomitant medications. The visit after treatment will assess NVP quality of life (NVPQoL), SAS, SDS and so on. Participants will be followed up 30 days after treatment. Primary outcomes is difference of the mean change in PUQE score from baseline to the last visit. Secondary outcomes were some core outcome set for hyperemesis gravidarum, including weight difference, quality of life (change in Global assessment of well-being, NVPQOL, VAS, SDS and SAS), pregnancy complication, treatment compliance, neonatal outcomes; area under the curve of PUQE score, effect of intervention on PUQE score reduction over treatment period and adverse events.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 352 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model Description: Two by two factorial design
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effectiveness of Acupuncture and Doxylamine/Pyridoxine for Moderate to Severe Nausea and Vomiting in Pregnancy: A Randomized Controlled Two-by-two Factorial Trial
Actual Study Start Date : June 21, 2020
Actual Primary Completion Date : June 23, 2021
Actual Study Completion Date : January 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Diclectin plus active acupuncture
Diclectin (combination of doxylamine succinate (10 mg) and pyridoxine hydrochloride (10 mg) , 2-4 tablets/day) + active acupuncture (30 min /every day).
Drug: Diclectin
Diclectin (combination of 10 mg doxylamine and 10 mg pyridoxine hydrochloride in a delayed release tablet) During the first two days, patients will start with an initial oral dose of 2 tablets at bedtime. If the symptoms assessed on the second day are not relieved, 3 tablets will be administered on the third day (1 tablet in the morning and 2 tablets at bedtime). On the third day if the symptoms are still not relieved, another tablet will be added in the afternoon on the fourth day (1 tablet in the morning, 1 tablet in the afternoon and 2 tablets at bedtime). Therefore, the maximum assigned dosage of Diclectin or placebo tablets do not exceed 4 tablets per day. The treatment duration will lasts for 14 days.

Device: Active acupuncture
Participants will receive active acupuncture every day for 2 consecutive weeks, a total of 14 sessions. The needle will be left for 30 minutes. After de qi induced by acupuncture, the paired electrodes of the electroacupuncture device will be connected to the needle handle horizontally (except for PC6).

Diclectin plus sham acupuncture
Diclectin (combination of doxylamine succinate (10 mg) and pyridoxine hydrochloride (10 mg), 2-4 tablets/day) + sham acupuncture (30 min /every day).
Drug: Diclectin
Diclectin (combination of 10 mg doxylamine and 10 mg pyridoxine hydrochloride in a delayed release tablet) During the first two days, patients will start with an initial oral dose of 2 tablets at bedtime. If the symptoms assessed on the second day are not relieved, 3 tablets will be administered on the third day (1 tablet in the morning and 2 tablets at bedtime). On the third day if the symptoms are still not relieved, another tablet will be added in the afternoon on the fourth day (1 tablet in the morning, 1 tablet in the afternoon and 2 tablets at bedtime). Therefore, the maximum assigned dosage of Diclectin or placebo tablets do not exceed 4 tablets per day. The treatment duration will lasts for 14 days.

Device: Sham acupuncture
Blunt-tipped placebo needles will be used. Participants will receive sham acupuncture every day for 2 consecutive weeks, a total of 14 sessions. The needle will be left for 30 minutes. After de qi induced by acupuncture, the paired electrodes of the electroacupuncture device will be connected to the needle handle horizontally (except for PC6). Then, the paired electrodes of the electroacupuncture device will be connected to the needle handle horizontally (except for PC6).

Placebo plus active acupuncture
Diclectin placebo (2-4 tablets/day) + active acupuncture (30 min / every day)
Drug: Diclectin placebo
Diclectin placebo will be packed and tested by a commercial pharmacy supply company specifically for this study. It have the same appearance, size, batch, odor, and taste compared with Diclectin. During the first two days, patients will start with an initial oral dose of 2 tablets at bedtime. If the symptoms assessed on the second day are not relieved, 3 tablets will be administered on the third day (1 tablet in the morning and 2 tablets at bedtime). On the third day if the symptoms are still not relieved, another tablet will be added in the afternoon on the fourth day (1 tablet in the morning, 1 tablet in the afternoon and 2 tablets at bedtime). Therefore, the maximum assigned dosage of placebo tablets do not exceed 4 tablets per day. The treatment duration will lasts for 14 days.

Device: Active acupuncture
Participants will receive active acupuncture every day for 2 consecutive weeks, a total of 14 sessions. The needle will be left for 30 minutes. After de qi induced by acupuncture, the paired electrodes of the electroacupuncture device will be connected to the needle handle horizontally (except for PC6).

Placebo plus sham acupuncture
Diclectin placebo (2-4 tablets/day) + sham acupuncture (30 min /every day)
Drug: Diclectin placebo
Diclectin placebo will be packed and tested by a commercial pharmacy supply company specifically for this study. It have the same appearance, size, batch, odor, and taste compared with Diclectin. During the first two days, patients will start with an initial oral dose of 2 tablets at bedtime. If the symptoms assessed on the second day are not relieved, 3 tablets will be administered on the third day (1 tablet in the morning and 2 tablets at bedtime). On the third day if the symptoms are still not relieved, another tablet will be added in the afternoon on the fourth day (1 tablet in the morning, 1 tablet in the afternoon and 2 tablets at bedtime). Therefore, the maximum assigned dosage of placebo tablets do not exceed 4 tablets per day. The treatment duration will lasts for 14 days.

Device: Sham acupuncture
Blunt-tipped placebo needles will be used. Participants will receive sham acupuncture every day for 2 consecutive weeks, a total of 14 sessions. The needle will be left for 30 minutes. After de qi induced by acupuncture, the paired electrodes of the electroacupuncture device will be connected to the needle handle horizontally (except for PC6). Then, the paired electrodes of the electroacupuncture device will be connected to the needle handle horizontally (except for PC6).




Primary Outcome Measures :
  1. Score change of pregnancy unique quantification of emesis (PUQE) scale from baseline to day 15 [ Time Frame: Baseline to day 15; Scores ranged 3 to 15, with higher scores indicating more ]
    Score change of pregnancy unique quantification of emesis (PUQE) scale from baseline to day 15


Secondary Outcome Measures :
  1. Score change of maternal weight from baseline to the last visit [ Time Frame: Baseline to day 15; no range of variation ]
    Score change of maternal weight from baseline to the last visit

  2. Change of electrolyte index (sodium) [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: mmol/L

  3. Change of electrolyte index (potassium) [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: mmol/L

  4. Change of electrolyte index (calcium) [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: mmol/L

  5. Change of electrolyte index (chlorine) [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: mmol/L

  6. Change of electrolyte index (phosphorus) [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: mmol/L

  7. Change of electrolyte index (magnesium) [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: mmol/L

  8. Change of electrolyte index (iron) [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: μmol/L

  9. Change of electrolyte index (zinc) [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: μmol/L

  10. Change of AST [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: U/L

  11. Change of ALT [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: U/L

  12. Change of ALP [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: U/L

  13. Change of creatinine [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: μmol/L

  14. Change of urea [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: mmol/L

  15. Change of TSH [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: mIU/L

  16. Change of free triiodothyronine [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: pmol/L

  17. Change of free thyroxine [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: pmol/L

  18. Change of vitamin b1 [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: ng/ml

  19. Change of vitamin b6 [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: ng/ml

  20. Change of vitamin b12 [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: ng/ml

  21. Change of cortisol [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: ug/dL

  22. Change of ghrelin [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: ng/ml

  23. Change of leptin [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: ng/ml

  24. Change of 5-hydroxytryptamine [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: ng/ml

  25. Change of substance P [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: pg/ml

  26. Change of arginine vasopressin plasma [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: pg/ml

  27. Change of GDF 15 [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: pg/ml

  28. Change of IGFBP 7 [ Time Frame: Baseline to day 15 ]
    Value changes from baseline to last Visit. Unit: ng/ml

  29. Intravenous fluid treatment during treatment [ Time Frame: Baseline to day 15 ]
    Intravenous fluid treatment during treatment

  30. Concomitant treatment [ Time Frame: Baseline to day 15 ]
    Concomitant treatment

  31. Hospital admission during treatment [ Time Frame: Baseline to day 15 ]
    Hospital admission during treatment

  32. Termination of pregnancy [ Time Frame: Data collected from baseline to the end of follow-up period (four weeks after the end of treatment). ]
    Termination of pregnancy. If the patient is suffering further aggravation of hyperemesis gravidarum, the termination of a wanted pregnancy will be done due to life in danger. Or congenital anomalies are found by ultrasound, the termination of a wanted pregnancy will be done.

  33. Maternal outcomes [ Time Frame: Data collected from baseline to 42 days after postpartum. ]
    Including pregnancy complications, termination of pregnancy and birth outcomes. Pregnancy complications including miscarriage (in the first trimester and in the second trimester), hypertensive disorders, and gestational diabetes; birth outcomes including live birth, vaginal delivery, cesarean section, gestational age, preterm, birth weight and small for gestational age.

  34. Patient satisfaction with treatment [ Time Frame: Baseline to day 15 ]
    Such as loss of confidence or intolerance to daily acupuncture and so on

  35. Treatment compliance [ Time Frame: Baseline to day 15 ]
    Such as the percentage of drug or needle used; or drug tablets or acupuncture sessions.

  36. Offspring outcomes [ Time Frame: Data collected from baseline to to 42 days after postpartum. ]
    Including fetal and neonatal congenital anomalies, fetal and neonatal mortality, neonatal hypoglycemia and NICU admission.

  37. Area under the curve (AUC) of PUQE score over treatment [ Time Frame: Baseline to day 15 ]
    Scores ranged 3 to 15, with higher scores indicating more severe NVP

  38. PUQE score reduction based on different TCM patterns [ Time Frame: Scores ranged 3 to 15, with higher reduction indicating the better ]
    PUQE score reduction based on different TCM patterns

  39. Adverse events and serious adverse events [ Time Frame: Baseline to the end of follow-up (four weeks after the end of treatment) ]
    The percentage of adverse events and serious adverse events

  40. Quality of life: NVPQoL [ Time Frame: Baseline to day 15 ]
    Range 30-210, high being poor QoL

  41. Quality of life: VAS [ Time Frame: Baseline to day 15 ]
    Ranged 0-10, high being more severe symptoms

  42. Quality of life: SDS [ Time Frame: Baseline to day 15 ]
    Range 25-10, high being more severe

  43. Quality of life: SAS [ Time Frame: Baseline to day 15 ]
    Range 25-100, high being more severe

  44. Quality of life: global assessment of well-being [ Time Frame: Baseline to day 15 ]
    Range 0-10, low being more severe

  45. PUQE score reduction at different levels of NVP [ Time Frame: Scores ranged 3 to 15, with higher reduction indicating the better ]
    PUQE score reduction at different levels of NVP



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Women with 20-45 years of age;
  2. PUQE score ≥6;
  3. 7-14 weeks of gestation with viable fetus inside the uterine cavity confirmed by ultrasound dating;
  4. Less than 20% weight loss.

Exclusion Criteria:

  1. Having major medical problems such as malignant tumor, acute or subacute severe hepatitis, severe aplastic anemia, idiopathic thrombocytopenic purpura, acute appendicitis, acute pancreatitis, TORCH syndrome, etc
  2. Having chronic medical conditions such as poorly controlled diabetes, coronary heart disease, uncontrolled hypertension, etc
  3. Coexistence of other diseases that cause vomiting such as infectious disease, gestational trophoblastic disease, etc
  4. Having asthma, increased intraocular pressure, narrow-angle glaucoma, narrow peptic ulcer, pyloric obstruction, bladder neck obstruction, etc
  5. Taking antiemetics such as vitamin B6, ondansetron, metoclopramide, prednisone, anti-vomiting Chinese medicine, etc., within the past week
  6. Receiving conservative treatment such as dietary and lifestyle modification
  7. Abnormal physical examination and laboratory tests (minor abnormalities in laboratory tests due to pregnancy vomiting, such as liver function and ions, are acceptable for inclusion)
  8. Having mental handicaps or psychological disorders
  9. Allergic to doxylamine, other ethanolamine-derived antihistamines, pyridoxine hydrochloride, or any inactive ingredient in diclectin
  10. Using monoamine oxidase inhibitors
  11. Driving or operating heavy machinery
  12. Using alcohol or other central nervous system inhibitors

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04401384


Locations
Layout table for location information
China, Heilongjiang
First Affiliated Hospital of Heilongjiang Chinese Medicine University
Harbin, Heilongjiang, China
Heilongjiang provincial hospital
Harbin, Heilongjiang, China
Hegang Maternal and Child Health Hospital
Hegang, Heilongjiang, China
Affiliated Hospital of Jiamusi Medical University
Jiamusi, Heilongjiang, China
Jiamusi Maternal and Child Health Hospital
Jiamusi, Heilongjiang, China
Jixi Maternal and Child Health Hospital
Jixi, Heilongjiang, China
Mudanjaing Maternal and Child Health Hospital
Mudanjiang, Heilongjiang, China
Shuangyashan Maternal and Child Health Hospital
Shuangyashan, Heilongjiang, China
China, Heilongjing
Suihua Maternal and Child Health Hospital
Suihua, Heilongjing, China
China, Henan
Luoyang Hospital of TCM
Luoyang, Henan, China
China, Jiangsu
Xuzhou Central Hospital
Xuzhou, Jiangsu, China
China, Jiangxi
Jiangxi Maternal and Child Health Hospital
Nanchang, Jiangxi, China
China, Ningxia Hui Autonomous Region
Ningxia Hui Autonomous Region Hospital of TCM
Yinchuan, Ningxia Hui Autonomous Region, China
Sponsors and Collaborators
Xiaoke Wu
Ningxia Hui Autonomous Region Hospital of TCM
Jiangxi Maternal and Child Health Hospital
Jixi Maternal and Child Health Hospital
Luoyang Hospital of TCM
Xuzhou Central Hospital
First Affiliated Hospital of Heilongjiang Chinese Medicine University
Shuangyashan Maternal and Child Health Hospital
Heilongjiang provincial hospital
Jiamusi Maternal and Child Health Hospital
Hegang Maternal and Child Health Hospital
Suihua Maternal and Child Health Hospital
Mudanjaing Maternal and Child Health Hospital
Affiliated Hospital of Jiamusi Medical University
Investigators
Layout table for investigator information
Study Chair: Xiaoke Wu, Ph.D First Affiliated Hospital of Heilongjiang University of Chinese Medicine
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Responsible Party: Xiaoke Wu, Director of obstetrics and Gynecology Department, Heilongjiang University of Chinese Medicine
ClinicalTrials.gov Identifier: NCT04401384    
Other Study ID Numbers: NVPAct
First Posted: May 26, 2020    Key Record Dates
Last Update Posted: April 4, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Xiaoke Wu, Heilongjiang University of Chinese Medicine:
Nausea and Vomiting of Pregnancy
PUQE
Acupuncture
Diclectin
Additional relevant MeSH terms:
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Nausea
Vomiting
Signs and Symptoms, Digestive
Pyridoxine
Dicyclomine, doxylamine, pyridoxine drug combination
Doxylamine
Dicyclomine
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Parasympatholytics
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Vitamin B Complex
Vitamins
Micronutrients