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CTRI Number  CTRI/2023/11/059872 [Registered on: 15/11/2023] Trial Registered Prospectively
Last Modified On:
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Ayurveda 
Study Design  Single Arm Study 
Public Title of Study   A study to evaluate the effect of an ayurvedic treatment protocol prior to in vitro fertilization in women with diminished ovarian reserve and understanding the molecular mechanisms involved. 
Scientific Title of Study   Role of an ayurvedic treatment protocol as a prerequisite for in vitro fertilization in women with diminished ovarian reserve: elucidating mechanistic insights incorporating multi-omics approaches 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Anjaly MV 
Designation  Associate Professor 
Affiliation  Amrita School of Ayurveda 
Address  Department of Prasuti tantra and Stree roga Amrita School of Ayurveda Amrita Vishwa Vidyapeetham Amritapuri campus Clappana PO, Kollam - 690525 Kerala

Kollam
KERALA
690525
India 
Phone  9495114149  
Fax    
Email  anjalymvarier@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Muralidharan V 
Designation  Assistant Professor 
Affiliation  Amrita School of Biotechnology 
Address  Amrita School of Biotechnology Amrita Vishwa Vidyapeetham Amritapuri campus Clappana PO, Kollam - 690525 Kerala

Kollam
KERALA
690525
India 
Phone  8589083013  
Fax    
Email  muralidharanv89@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Dr Muralidharan V 
Designation  Assistant Professor 
Affiliation  Amrita School of Biotechnology 
Address  Amrita School of Biotechnology Amrita Vishwa Vidyapeetham Amritapuri campus Clappana PO, Kollam - 690525 Kerala

Kollam
KERALA
690525
India 
Phone  8589083013  
Fax    
Email  muralidharanv89@gmail.com  
 
Source of Monetary or Material Support  
Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Ponekkara P.O. Kochi, Kerala 682 041, India 
Amrita School of Ayurveda, Amrita Vishwa Vidyapeetham, Amritapuri campus, Clappana PO, Kollam - 690525, Kerala, India 
Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri campus, Clappana PO, Kollam - 690525, Kerala, India 
Indian Council of Medical Research, Department of Health Research, Ministry of Health & Family Welfare Government of India, Ansari Nagar, New Delhi - 110029, India 
 
Primary Sponsor  
Name  Amrita School of Ayurveda 
Address  Amrita School of Ayurveda, Amrita Vishwa Vidyapeetham, Amritapuri campus, Clappana PO, Kollam - 690525, Kerala, India 
Type of Sponsor  Private medical college 
 
Details of Secondary Sponsor  
Name  Address 
Amrita Institute of Medical Sciences  Department of Reproductive Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Ponekkara P.O. Kochi, Kerala 682 041, India 
Amrita School of Biotechnology  Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri campus, Clappana PO, Kollam - 690525, Kerala, India 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Anjaly MV  Amrita School of Ayurveda  Amrita Vishwa Vidyapeetham, Amritapuri campus, Clappana PO, Kollam - 690525, Kerala, India
Kollam
KERALA 
9495114149

anjalymvarier@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Amrita Institute of Medical Sciences Institutional Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition:N979||Female infertility, unspecified. Ayurveda Condition: ARTAVAKSHAYAH,  
 
Intervention / Comparator Agent  
snoIntervention/ComparatorTypeDrug-TypeProcedure NameDetails
1Intervention ArmProcedure-uttara-bastiH, उत्तर-बस्तिः (Procedure Reference: Ashtanga Hridaya, Procedure details: 3 - 5 ml of Mahānārayaṇataila will be introduced into the uterine cavity on the day of Niruha vasti)
(1) Medicine Name: Mahanarayana Taila, Reference: Sahasrayoga, Route: Vaginal, Dosage Form: Taila, Dose: 5(ml), Frequency: od, Duration: 3 Days
2Intervention ArmProcedure-yoga-bastiH, योग-बस्तिः (Procedure Reference: Charaka Samhita, Procedure details: Nirūhabasti with 750 ml of Mustadiyapanabasti & Anuvāsanabasti with 150 ml of Mahānārayaṇataila will be done on alternate days)
(1) Medicine Name: Mahanarayana Taila, Reference: Sahasrayoga, Route: Rectal, Dosage Form: Taila, Dose: 150(ml), Frequency: od, Duration: 5 Days
3Intervention ArmProcedure-aBya~ggaH, अभ्यंग  (Procedure Reference: Ashtanga Hridaya, Procedure details: Abhyanga & svedana will be done for three days with Dhanwantara taila)
(1) Medicine Name: Dhanwantara taila, Reference: Ashtanga Hridaya, Route: Topical, Dosage Form: Taila, Dose: 100(ml), Frequency: od, Duration: 3 Days
4Intervention ArmProcedure-svedanam, स्वेदनम् (Procedure Reference: Ashtanga Hridaya, Procedure details: Following Abhyanga Svedana will be done as a purva karma of shodhana)
(1) Medicine Name: Dhanwantara taila, Reference: Ashtanga Hridaya, Route: Topical, Dosage Form: Taila, Dose: 100(ml), Frequency: od, Duration: 3 Days
5Intervention ArmProcedure-vamana-karma/ pracCardanam, वमन-कर्म/ प्रच्छर्दनम् (Procedure Reference: Ashtanga Hridaya, Procedure details: Mridu Vamana will be done according to the patient condition.)
(1) Medicine Name: Yashtimadhu, Madana phala, vacha, Reference: Susrutha Samhita, Route: Oral, Dosage Form: Churna/ Powder, Dose: 10(g), Frequency: od, Duration: 1 Days
6Intervention ArmProcedure-virecana-karma, विरेचन-कर्म (Procedure Reference: Ashtanga Hridaya, Procedure details: Virechana will be done with Avipathy Churna 30g at preferably 7 am after snehana & svedana)
(1) Medicine Name: Avipathy churna, Reference: Sahasrayoga, Route: Oral, Dosage Form: Churna/ Powder, Dose: 30(g), Frequency: od, Duration: 1 Days
7Intervention ArmProcedure-dIpana , दीपन (Procedure Reference: Ashtanga Hridaya, Procedure details: As a purva karma of Shodhana, 5g of Vaiswanara churna will be given twice daily before food with warm water for a maximum of two days))
(1) Medicine Name: Vaiswanara Churna, Reference: Sahasrayoga, Route: Oral, Dosage Form: Churna/ Powder, Dose: 5(g), Frequency: bd, Duration: 2 Days
8Intervention ArmProcedure-pAcana, पाचन (Procedure Reference: Ashtanga Hridaya, Procedure details: As a purva karma of Shodhana, 5g of Vaiswanara chirna will be given twice daily before food with warm water for a maximum of two days) )
(1) Medicine Name: Vaiswanara Churna, Reference: Sahasrayoga, Route: Oral, Dosage Form: Churna/ Powder, Dose: 5(g), Frequency: bd, Duration: 2 Days
9Intervention ArmDrugClassical(1) Medicine Name: Mahanarayana Taila, Reference: Sahasrayoga, Route: Oral, Dosage Form: Taila, Dose: 10(ml), Frequency: od, Bhaishajya Kal: Abhakta, Duration: 1 Months, anupAna/sahapAna: Yes(details: -ushna jala), Additional Information: -
(2) Medicine Name: Kalyanaka gritha, Reference: Ashtanga Hridaya, Route: Oral, Dosage Form: Ghrita, Dose: 10(ml), Frequency: od, Bhaishajya Kal: Abhakta, Duration: 1 Months, anupAna/sahapAna: Yes(details: -ushna jala), Additional Information: -
(3) Medicine Name: Phala Sarpi, Reference: Sahasrayoga, Route: Oral, Dosage Form: Ghrita, Dose: 10(ml), Frequency: od, Bhaishajya Kal: Abhakta, Duration: 1 Months, anupAna/sahapAna: Yes(details: -ushna jala), Additional Information: -
(4) Medicine Name: Satapushpa choorna, Reference: Kashyapa Samhita, Route: Oral, Dosage Form: Churna/ Powder, Dose: 5(g), Frequency: bd, Bhaishajya Kal: Abhakta, Duration: 1 Months, anupAna/sahapAna: Yes(details: -ushna jala), Additional Information: -
(5) Medicine Name: Hinguvachadi choorna, Reference: Ashtanga Hridaya, Route: Oral, Dosage Form: Churna/ Powder, Dose: 5(g), Frequency: bd, Bhaishajya Kal: Abhakta, Duration: 1 Months, anupAna/sahapAna: Yes(details: -ushna jala), Additional Information: -
10Intervention ArmProcedure-acCasnehaH, अच्छस्नेहः (Procedure Reference: Ashtanga Hridaya, Procedure details: Shodhananga Snehapāna with appropriate ghee or oil. Ārohaṇakrama (Escalation of dose) will be done after assessing the Agni & koṣṭha (Digestion) of participant)
(1) Medicine Name: Mahanarayana Taila, Reference: Sahasrayoga, Route: Oral, Dosage Form: Taila, Dose: 25(ml), Frequency: od, Duration: 7 Days
(2) Medicine Name: Kalyanaka Gritha, Reference: Ashtanga Hridaya, Route: Oral, Dosage Form: Ghrita, Dose: 25(ml), Frequency: od, Duration: 7 Days
(3) Medicine Name: Phalasarpi, Reference: Ashtanga Hridaya, Route: Oral, Dosage Form: Ghrita, Dose: 25(ml), Frequency: od, Duration: 7 Days
 
Inclusion Criteria  
Age From  25.00 Year(s)
Age To  40.00 Year(s)
Gender  Female 
Details  1)Participant willing and able to give informed consent for participation in the trial.
2)Diagnosed with Diminished ovarian reserve (serum AMH <1.1 ng/ml, AFC < 7 follicles)
3)Poor ovarian response in the prior IVF cycle
 
 
ExclusionCriteria 
Details  1)Diagnosed of genetic disorders
2)Undergoing treatment for malignancy
3)History of oophorectomy
 
 
Method of Generating Random Sequence   Not Applicable 
Method of Concealment   Not Applicable 
Blinding/Masking   Not Applicable 
Primary Outcome  
Outcome  TimePoints 
1) Improvement in Ultrasonography count of ovarian antral follicles, Antral follicle count (AFC) - on Day 2/3 of the menstrual cycle
2)Improvement in serum anti-Mullerian hormone (AMH) – Day 2/3 of the Menstrual Cycle 
Assessment before treatment (BT) will be done during recruitment and post assessment after treatment (AT) will be done after two months of Ayurvedic treatment.  
 
Secondary Outcome  
Outcome  TimePoints 
Multi omics analysis of follicular fluid - (Treatment group - 10; after two months of Ayurveda treatment and Control group - 10).  On the day of oocyte retrieval during In Vitro fertilization.  
 
Target Sample Size   Total Sample Size="40"
Sample Size from India="40" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   01/02/2024 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="3"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

The trial is designed as single arm pre-and post- clinical study. Study setting - Amrita Fertility Centre and Amrita School of Ayurveda, Amrita Vishwa Vidyapeetham. 

Women diagnosed with DOR (AFC <5–7 follicles and AMH <0.5–1.1 ng/ml) undergoing IVF cycles will be screened at Amrita Fertility Centre. After due consent, these patients will be subjected to Ayurvedic treatment protocol at Amrita School of Ayurveda. Assessment criteria - Serum AMH and Ultrasonography count of ovarian Antral Follicle on Day 2/3 of the menstrual cycle. Intervention at Amrita School of Ayurveda - The therapeutic plan will be initially performed through Sodhana cikitsa (cleansing therapy), during which the patient will be admitted to the hospital for 21 days. It will be followed by Shamana cikitsa (oral medication) for 1 month. Sodhana chikitsa includes Accha Snehapāna (intake of oil/ghee) and Mridu Vamana/Virechana (emesis/purgation). In the final phase, the patient will be subjected to Yoga Basti and Uttara Basti (medicated enema through the anal route and vagina). After completing shodhana chikitsa shamana chikitsa will be done. After undergoing Ayurveda treatment for two months, participants will be sent back to Amrita Fertility Centre for post- assessment and further fertility treatments, during which follicular fluid will be collected for multi-omics analysis.

Study tools -  Ultrasonography count of ovarian antral follicles, Antral follicle count (AFC) on Day 2/3 of menstrual cycle and Serum test of anti-Mullerian hormone (AMH) on Day 2/3 of menstrual cycle 

Sample size -  40 women diagnosed with DOR satisfying inclusion and exclusion criteria after consent will be recruited to the study for Ayurvedic treatment protocol, Follicular fluid will be collected from 20 patients for multi-omics analysis (Treatment group - 10 and Control group -  10)

Study Interventions

Treatment protocol and Interventions – Sodhana chikitsa

Treatment procedure

Method of administration

Treatment duration

Dipana, pacana with Vaisvanara churna (preparatory procedure)

5g twice daily before food with warm water

Day 1–2

 

 

Snehapana with appropriate ghee or oil

Arohanakrama (Escalation of dose) after assessing the Agni and koshta (Digestion)

Day 3–8

 

 

Snehana and svedana (Oleation and sweating treatment)

Sarvanga abhyanga (whole body massage)with Dhanvantara taila followed by nadi sveda (sweating treatment)

Day 9 – 11

 

 

 

Mridu vamana or

Mriduvirecana with Avipatti choorna

 

30 g given at 7 am

Day 10 or

Day 11

 

Yogabasti (medicated enema through anal route)

Niruhabasti with 750 ml of Mustadiyapanabasti and Anuvasanabasti with 150 ml of Mahanarayana taila

Day 13–20

 

 

 

 

Uttarabasti (medicated enema through vaginal route)

With 3 ml Mahanarayana taila into the uterine cavity on the day of Niruha vasti

 


Shamana cikitsa (oral medications)

·      Kalyanaka Ghrita/Phala sarpi – Ghrita formulation - 10ml once daily, orally

·      Mahanarayana taila– Taila formulation - 10ml once daily, orally

·      Satapushpa choorna/Hinguvachadi choorna– choorna formulation - 5gm twice daily, orally

 
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