PRP-E: Platelet-rich Plasma (PRP) for Endometrial Regeneration and Repair

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02825849
• Collaborator: (none)
• Enrollment: 27
• Location: 1
• Arms: 2
• Duration (Months): 33
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

Patients with intrauterine adhesions (Asherman's Syndrome) and persistent thin endometrial lining in in vitro fertilization (IVF) treatment programs, particularly those resistant to standard therapies, present a significant clinical challenge. The aim of this trial is to assess if intrauterine administration of platelet rich plasma (PRP) improves endometrial lining thickness in patients with thin lining or Asherman's Syndrome.

Condition or Disease	Intervention/Treatment	Phase
Infertility; Asherman's Syndrome	Biological: Intrauterine infusion of platelet rich plasma	Phase 2

Detailed Description

BACKGROUND:

There is a need for new and more effective therapies for patients with intrauterine adhesions (Asherman's Syndrome) and persistent thin endometrial lining in in vitro fertilization (IVF) treatment programs, particularly for patients resistant to standard therapies

HYPOTHESIS:

Platelet rich plasma stimulates cellular processes involved in endometrial regeneration relevant to management of a thin lining or intrauterine scarring.

PRIMARY AIMS:

• To measure the change in endometrial lining thickness

SECONDARY AIMS:

• To determine if fertility is improved in patients receiving platelet rich plasma (PRP):

1. In patients with thin lining undergoing frozen embryo transfer (FET), to determine:

• clinical pregnancy rate

1. In patients with Asherman's Syndrome, to determine:

• the chance of spontaneous pregnancy

Any adverse effects of study arm will be monitored and reported as appropriate.

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: During Study Period #1: Subjects were randomized to receive either PRP or standard care. A total of 13 subjects were randomized. The study design was then altered to remove randomization (10/4/2018). All patients in Study Period #2 received PRP. An additional 14 subjects were enrolled in Study Period #2.During Study Period #1: Subjects were randomized to receive either PRP or standard care. A total of 13 subjects were randomized. The study design was then altered to remove randomization (10/4/2018). All patients in Study Period #2 received PRP. An additional 14 subjects were enrolled in Study Period #2.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Platelet-rich Plasma (PRP) for Endometrial Regeneration and Repair: a Prospective Randomised Pilot Study
• Study Start Date: Nov 1, 2016
• Actual Primary Completion Date: Aug 1, 2019
• Actual Study Completion Date: Aug 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PRP intrauterine infusion Intrauterine infusion of platelet rich plasma in combination with standard treatment, in patients with Asherman's Syndrome or thin uterine lining in frozen embryo transfer cycles	Biological: Intrauterine infusion of platelet rich plasma; Patients randomized to study group will have 30cc of blood drawn with isolation of platelet rich plasma (PRP) per standard manufacturer's protocol, with subsequent intrauterine infusion of this autologous PRP.; Other Names: PRP
No Intervention: Control group with standard treatment only Patients with Asherman's Syndrome or thin uterine lining in frozen embryo transfer cycles undergoing standard treatment protocols

Outcome Measures

Primary Outcome Measures

1. Endometrial Thickness [3-30 days after treatment]

   Endometrial thickness will be measured using transvaginal ultrasound per standard protocol

Secondary Outcome Measures

1. Number of Participants With Ultrasound Confirmed Clinical Pregnancies [at least 7 weeks after treatment]

   Defined by ultrasound confirmed pregnancies per total participants in each arm

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 43 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Persistent thin lining < 6mm on >1 cycle in previous IVF or FET cycle OR moderate-to-severe Asherman's syndrome

Exclusion Criteria:

• Age <18 years old or >43 years old,

• Pregnancy,

• Diagnosis of cancer,

• Hb <11 g/dL, platelets <150,000/mm3,

• Anticoagulation,

• NSAIDs in the 10 days before procedure

• Any significant comorbidity or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.

• Incision in the uterus: myomectomy; cesarean section

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Francisco - Center for Reproductive Health	San Francisco	California	United States	94158

Sponsors and Collaborators

• University of California, San Francisco

Investigators

• Principal Investigator: Heather G. Huddleston, MD, University of California, San Francisco

Study Documents (Full-Text)

• Statistical Analysis Plan - Nov 15, 2020
• Study Protocol - Oct 25, 2019
• Informed Consent Form - Oct 24, 2019

More Information

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT02825849
• Other Study ID Numbers: 16-19764
• First Posted: Jul 7, 2016
• Last Update Posted: Feb 9, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by University of California, San Francisco: endometrium; thin uterine lining; uterine scarring
• Additional relevant MeSH terms: Infertility; Gynatresia

Study Results

Participant Flow

Arm/Group Title	PRP Intrauterine Infusion	Control Group With Standard Treatment Only
Arm/Group Description	Intrauterine infusion of platelet rich plasma in combination with standard treatment, in patients with Asherman's Syndrome or thin uterine lining in frozen embryo transfer cycles Intrauterine infusion of platelet rich plasma: Patients randomized to study group will have 30cc of blood drawn with isolation of platelet rich plasma (PRP) per standard manufacturer's protocol, with subsequent intrauterine infusion of this autologous PRP.	Patients with Asherman's Syndrome or thin uterine lining in frozen embryo transfer cycles undergoing standard treatment protocols
Period Title: Overall Study
STARTED	22	5
COMPLETED	22	5
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	PRP Intrauterine Infusion	Control Group With Standard Treatment Only	Total
Arm/Group Description	Intrauterine infusion of platelet rich plasma in combination with standard treatment, in patients with Asherman's Syndrome or thin uterine lining in frozen embryo transfer cycles Intrauterine infusion of platelet rich plasma: Patients randomized to study group will have 30cc of blood drawn with isolation of platelet rich plasma (PRP) per standard manufacturer's protocol, with subsequent intrauterine infusion of this autologous PRP.	Patients with Asherman's Syndrome or thin uterine lining in frozen embryo transfer cycles undergoing standard treatment protocols	Total of all reporting groups
Overall Participants	22	5	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.9 (3.2)	35.6 (6.3)	37.5 (3.9)
Sex: Female, Male (Count of Participants)
Female	22 100%	5 100%	27 100%
Male	0 0%	0 0%	0 0%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Count of Participants)
United States	22 100%	5 100%	27 100%
Endometrial Thickness (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	6.3 (2.3)	4.3 (1.2)	5.9 (2.3)
Ashermans score on hysteroscopy (score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score]	5.6 (1.17)	5.8 (2.49)	5.67 (1.63)

Outcome Measures

1. Primary Outcome

Title	Endometrial Thickness
Description	Endometrial thickness will be measured using transvaginal ultrasound per standard protocol
Time Frame	3-30 days after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PRP Intrauterine Infusion	Control Group With Standard Treatment Only
Arm/Group Description	Intrauterine infusion of platelet rich plasma in combination with standard treatment, in patients with Asherman's Syndrome or thin uterine lining in frozen embryo transfer cycles Intrauterine infusion of platelet rich plasma: Patients randomized to study group will have 30cc of blood drawn with isolation of platelet rich plasma (PRP) per standard manufacturer's protocol, with subsequent intrauterine infusion of this autologous PRP.	Patients with Asherman's Syndrome or thin uterine lining in frozen embryo transfer cycles undergoing standard treatment protocols
Measure Participants	22	5
Mean (Standard Deviation) [cm]	6.4 (2.4)	5.2 (2.3)

2. Secondary Outcome

Title	Number of Participants With Ultrasound Confirmed Clinical Pregnancies
Description	Defined by ultrasound confirmed pregnancies per total participants in each arm
Time Frame	at least 7 weeks after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PRP Intrauterine Infusion	Control Group With Standard Treatment Only
Arm/Group Description	Intrauterine infusion of platelet rich plasma in combination with standard treatment, in patients with Asherman's Syndrome or thin uterine lining in frozen embryo transfer cycles Intrauterine infusion of platelet rich plasma: Patients randomized to study group will have 30cc of blood drawn with isolation of platelet rich plasma (PRP) per standard manufacturer's protocol, with subsequent intrauterine infusion of this autologous PRP.	Patients with Asherman's Syndrome or thin uterine lining in frozen embryo transfer cycles undergoing standard treatment protocols
Measure Participants	22	5
Count of Participants [Participants]	12 54.5%	3 60%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRP Intrauterine Infusion, Control Group With Standard Treatment Only
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.824
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	Adverse events were collected for up to 365 days after study treatment
Arm/Group Title	PRP Intrauterine Infusion		Control Group With Standard Treatment Only
Arm/Group Description	Intrauterine infusion of platelet rich plasma in combination with standard treatment, in patients with Asherman's Syndrome or thin uterine lining in frozen embryo transfer cycles Intrauterine infusion of platelet rich plasma: Patients randomized to study group will have 30cc of blood drawn with isolation of platelet rich plasma (PRP) per standard manufacturer's protocol, with subsequent intrauterine infusion of this autologous PRP.		Patients with Asherman's Syndrome or thin uterine lining in frozen embryo transfer cycles undergoing standard treatment protocols
All Cause Mortality
	PRP Intrauterine Infusion		Control Group With Standard Treatment Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/5 (0%)
Serious Adverse Events
	PRP Intrauterine Infusion		Control Group With Standard Treatment Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	PRP Intrauterine Infusion		Control Group With Standard Treatment Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/5 (0%)

Limitations/Caveats

The study was a pilot study and was not adequately powered to detect a difference. In addition the study was closed prior to full enrollment.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.