Re-establishment of Ovarian Hormonal Function, Delay of Menopause, or Reversal of Early Menopause With High Density (HD PRP), tSVF + PRP, or Cell Enriched tSVF + PRP by Ultrasound Guided Ovarian Injection
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Patient Safety For Procedure
研究概览
简要总结
Trial of imaging guided intra-ovarian injection to improve ovarian function in clinical settings of Premature Ovarian Failure, Perimenopausal and /or early postmenopausal symptomatology and related hormonal deficiencies. The study will compare the effectiveness of autologous Platelet Rich Plasma alone versus Stromal Vascular Fraction (tSVF and/or cellular stromal vascular fraction (cSVF) in combination with Platelet Rich Plasma as regards efficacy and duration of ovarian reactivation in women with acquired Premature Ovarian Failure, Menopausal, and Perimenopausal women.
详细描述
Intra-ovarian placement of platelet rich plasma (PRP) has already been demonstrated in several series to return peri-menopausal and early post-menopausal hormone levels towards pre-menopausal levels and pre-menopausal cyclic behavior, even resulting in pregnancies and deliveries of healthy infants. The intent of this trial is to evaluate the utility of PRP to improve hormonal status and clinical symptomatology in peri-menopausal and early post-menopausal women, and in women with non-Turner's premature ovarian failure, by documenting the improvements in biochemical/hormonal parameters, bone density, and physical and mental health related quality of life, as well as comparing the duration and effectiveness of this PRP procedure with the intra-ovarian placement of biocellular physiologically active cellular and cytokine elements contained within the adipose tissue-derived Stromal Vascular Fraction (tSVF).
It should be noted that rate of loss of bone density in women is maximal in the 12 months prior and 24 months following menopause. The absolute and relative percentage amounts of body fat and muscle change in adverse ways - with increasing fat and falling muscle bulk, with the most dramatic changes also occurring in the menopausal transition period. This study therefore provides the potential to document measurable cessation of bone density loss or reduction in rate of bone density loss compared to well established known patterns and historical controls as a result of the proposed relatively innocuous interventions. The same technology to be used for bone density evaluation, single photon absorptiometry, will also be used to quantify fat versus muscle body composition at baseline and 18 months.
SVF can be further characterized as either cellular SVF or tissue SVF (cSVF or tSVF). Tissue SVF (tSVF) is obtained by a small volume manual closed syringe microcannula aspiration of subcutaneous fatty tissue (approximately 10+ teaspoons), followed by closed system decanting to remove the infranatant fluids followed by emulsification of the remnant to the required degree of homogeneity and reduced particulate size to permit injection through a conventional gauge needle bores. Tissue SVF is characterized by retention of a proportion of the non-cellular matrix of collagenous and fine vascular remnants, which together form a matrix that retains and provides structure to the biocellular elements that are embedded within. Cellular SVF (cSVF) begins with the same mini-aspiration, but is characterized by closed system centrifugation, followed enzymatic digestion to isolate./concentrate the cellular SVF (cSVF). Following enzyme neutralization and rinsing, the resultant concentrate of viable stem/stromal nucleated cells, are prepared for guided placement into the ovarian parenchymal tissue. A sample of each injectate is tested and quantified using standard laser flow cytometry, including viability and numbers of cells within each sample.
The study includes use of PRP (Emcyte II Pure PRP, Florida, USA) PRP per manufacturer's instructions) alone as control in first treatment limb (ARM), which will volumetrically be the same as the other injectates, for guided placement documented within the ovaries. A comparative second ARM composed of PRP will be combined with emulsified tSVF (Sterile Tulip Nanofat Disposable, San Diego, California (CA), USA) . In a third ARM, PRP plus emulsified tSVF will be combined with both concentrated cSVF. This arm is to determine effects of higher cellular concentration than achieved in second ARM using the cellular concentrates achieve using the Centricyte 1000 (Healeon Medical Inc, Newbury Park, CA, USA). The primary outcomes for each of these optional procedures will be compared, and evaluated as to safety, clinical efficacy in enhancing return of ovarian function to determine the preferred methodology to achieve maximal outcomes.
Baseline and monitored patient characteristics are as follows:
研究设计
- 研究类型
- 干预性
- 分配方式
- 非随机
- 干预模型
- 平行分组
- 主要目的
- 治疗
- 盲法
- 开放（无盲法）
入排标准
- 年龄范围
- 35 Years 至 60 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- Symptomatology or hormonal derangement for at least 6 months
- Stopped Hormonal Replacement Therapy (HRT) for at least 3 months prior to intervention
- Stopped Botanotherapy / Danazol for 3 months
- Willing to comply with study requirements, including avoiding HRT, Botanotherapy, Danazol for at least 12 months post intervention.
- Women over the age of 35
- Presence of at least one ovary
- Agree to report any pregnancy to the research staff immediately.
- Willing and able to comply with study requirements.
排除标准
- Current or previous Immune Globulin A (IgA) deficiency
- Current or previous premature ovarian failure due to a genetic origin, such as Turner's Syndrome or chromosomal abnormality
- Current or previous injuries or adhesions to the pelvis or ovaries
- Current and ongoing pregnancy
- Current and ongoing anticoagulant use
- Known bleeding diathesis
- Current and ongoing major Mental health disorder that precludes participation in the study
- Current and ongoing active substance abuse or dependence
- Prior or current ovarian malignancy, or known genetic mutation
- Current and ongoing chronic pelvic pain other than dyspareunia or vulval/vaginal integument disorders
- History of endometriosis
- Current diagnosis of cancer or active cancer within last 24 months
- Ovarian inaccessibility determined by endovaginal sonography
- Current or previous premature ovarian failure
- Active, untreated Endocrinologic disorders (uncompensated thyroid dysfunction, insulin dependant diabetes (type 1, type2)
- Body Mass Index (BMI) >30 kg/m2
- Systemic autoimmune disorder
- Know Polycystic Ovarian Syndrome
- Unwilling to terminate ovarian pharmaceuticals or exogenous hormone treatments 3 months prior to entering study, and to avoid exogenous hormones for duration of study
研究组 & 干预措施
ARM 1 Platelet Rich Plasma
Blood draw, processing of PRP, white blood cell poor, high platelet multiple >/= 4, e.g. (Emcyte II Pure PRP) Endovaginal ultrasound guided intra-ovarian placement into ovarian parenchyma, preferably both if accessible.
干预措施: lipoaspiration harvest tSVF (Procedure)
ARM 1 Platelet Rich Plasma
Blood draw, processing of PRP, white blood cell poor, high platelet multiple >/= 4, e.g. (Emcyte II Pure PRP) Endovaginal ultrasound guided intra-ovarian placement into ovarian parenchyma, preferably both if accessible.
干预措施: Platelet Rich Plasma (Procedure)
ARM 2 emulsified tSVF and PRP
Blood draw, processing of PRP, white blood cell poor, high platelet multiple >/= 4, e.g. Emcyte PRP Lipoaspiration utilizing closed microcannula harvesting of small volume (Tulip tumescent fluid infiltrator and Tulip Harvester). Decanting of free lipid. Emulsification of adipose tissue into tSVF (Tulip Nanofat device). Blending of Nanofat with PRP at a 3:1 ratio.
Endovaginal ultrasound guided intra-ovarian placement into ovary, preferably both if accessible.
干预措施: Endovaginal Ultrasound (Procedure)
ARM 2 emulsified tSVF and PRP
Blood draw, processing of PRP, white blood cell poor, high platelet multiple >/= 4, e.g. Emcyte PRP Lipoaspiration utilizing closed microcannula harvesting of small volume (Tulip tumescent fluid infiltrator and Tulip Harvester). Decanting of free lipid. Emulsification of adipose tissue into tSVF (Tulip Nanofat device). Blending of Nanofat with PRP at a 3:1 ratio.
Endovaginal ultrasound guided intra-ovarian placement into ovary, preferably both if accessible.
干预措施: emulsification tSVF (Device)
ARM 1 Platelet Rich Plasma
Blood draw, processing of PRP, white blood cell poor, high platelet multiple >/= 4, e.g. (Emcyte II Pure PRP) Endovaginal ultrasound guided intra-ovarian placement into ovarian parenchyma, preferably both if accessible.
干预措施: Endovaginal Ultrasound (Procedure)
ARM 2 emulsified tSVF and PRP
Blood draw, processing of PRP, white blood cell poor, high platelet multiple >/= 4, e.g. Emcyte PRP Lipoaspiration utilizing closed microcannula harvesting of small volume (Tulip tumescent fluid infiltrator and Tulip Harvester). Decanting of free lipid. Emulsification of adipose tissue into tSVF (Tulip Nanofat device). Blending of Nanofat with PRP at a 3:1 ratio.
Endovaginal ultrasound guided intra-ovarian placement into ovary, preferably both if accessible.
干预措施: lipoaspiration harvest tSVF (Procedure)
ARM 3 emulsified tSVF and PRP, enriched with cSVF
Blood draw, processing of PRP, white blood cell poor, high platelet multiple >/= 4, e.g. Emcyte PRP tSVF preparation: Lipoaspiration utilizing closed microcannula harvesting of small volume (Tulip tumescent fluid infiltrator and Tulip Harvester). Decanting of free lipid. Emulsification of adipose tissue (Tulip Nanofat device).
cSVF preparation: lipoaspiration as above. Isolation and Concentration of cellular stromal vascular fraction (cSVF) using a Healeon Medical CentriCyte 1000 centrifuge, incubator and shaker plate with sterile Liberase enzyme (Roche Medical) per manufacturer protocol. Quantification of viable nucleated cell count with flow cytometry. Addition of pellet of viable nucleated cells to tSVF.
Blending of tSVF/cSVF emulsion with PRP at a 3:1 ratio. Endovaginal ultrasound guided intra-ovarian placement into ovary, preferably both if accessible.
Intervention:
干预措施: Normal Saline (NS) .9% 10 mL Injection (Drug)
ARM 4 Intra-ovarian guided placement
Specifically designed 23 gauge modified oocyte harvester needle for ultrasound guided placement
干预措施: Endovaginal Ultrasound (Procedure)
ARM 2 emulsified tSVF and PRP
Blood draw, processing of PRP, white blood cell poor, high platelet multiple >/= 4, e.g. Emcyte PRP Lipoaspiration utilizing closed microcannula harvesting of small volume (Tulip tumescent fluid infiltrator and Tulip Harvester). Decanting of free lipid. Emulsification of adipose tissue into tSVF (Tulip Nanofat device). Blending of Nanofat with PRP at a 3:1 ratio.
Endovaginal ultrasound guided intra-ovarian placement into ovary, preferably both if accessible.
干预措施: Platelet Rich Plasma (Procedure)
ARM 3 emulsified tSVF and PRP, enriched with cSVF
Blood draw, processing of PRP, white blood cell poor, high platelet multiple >/= 4, e.g. Emcyte PRP tSVF preparation: Lipoaspiration utilizing closed microcannula harvesting of small volume (Tulip tumescent fluid infiltrator and Tulip Harvester). Decanting of free lipid. Emulsification of adipose tissue (Tulip Nanofat device).
cSVF preparation: lipoaspiration as above. Isolation and Concentration of cellular stromal vascular fraction (cSVF) using a Healeon Medical CentriCyte 1000 centrifuge, incubator and shaker plate with sterile Liberase enzyme (Roche Medical) per manufacturer protocol. Quantification of viable nucleated cell count with flow cytometry. Addition of pellet of viable nucleated cells to tSVF.
Blending of tSVF/cSVF emulsion with PRP at a 3:1 ratio. Endovaginal ultrasound guided intra-ovarian placement into ovary, preferably both if accessible.
Intervention:
干预措施: Cellular Isolation cSVF (Device)
ARM 3 emulsified tSVF and PRP, enriched with cSVF
Blood draw, processing of PRP, white blood cell poor, high platelet multiple >/= 4, e.g. Emcyte PRP tSVF preparation: Lipoaspiration utilizing closed microcannula harvesting of small volume (Tulip tumescent fluid infiltrator and Tulip Harvester). Decanting of free lipid. Emulsification of adipose tissue (Tulip Nanofat device).
cSVF preparation: lipoaspiration as above. Isolation and Concentration of cellular stromal vascular fraction (cSVF) using a Healeon Medical CentriCyte 1000 centrifuge, incubator and shaker plate with sterile Liberase enzyme (Roche Medical) per manufacturer protocol. Quantification of viable nucleated cell count with flow cytometry. Addition of pellet of viable nucleated cells to tSVF.
Blending of tSVF/cSVF emulsion with PRP at a 3:1 ratio. Endovaginal ultrasound guided intra-ovarian placement into ovary, preferably both if accessible.
Intervention:
干预措施: emulsification tSVF (Device)
ARM 2 emulsified tSVF and PRP
Blood draw, processing of PRP, white blood cell poor, high platelet multiple >/= 4, e.g. Emcyte PRP Lipoaspiration utilizing closed microcannula harvesting of small volume (Tulip tumescent fluid infiltrator and Tulip Harvester). Decanting of free lipid. Emulsification of adipose tissue into tSVF (Tulip Nanofat device). Blending of Nanofat with PRP at a 3:1 ratio.
Endovaginal ultrasound guided intra-ovarian placement into ovary, preferably both if accessible.
干预措施: Normal Saline (NS) .9% 10 mL Injection (Drug)
ARM 3 emulsified tSVF and PRP, enriched with cSVF
Blood draw, processing of PRP, white blood cell poor, high platelet multiple >/= 4, e.g. Emcyte PRP tSVF preparation: Lipoaspiration utilizing closed microcannula harvesting of small volume (Tulip tumescent fluid infiltrator and Tulip Harvester). Decanting of free lipid. Emulsification of adipose tissue (Tulip Nanofat device).
cSVF preparation: lipoaspiration as above. Isolation and Concentration of cellular stromal vascular fraction (cSVF) using a Healeon Medical CentriCyte 1000 centrifuge, incubator and shaker plate with sterile Liberase enzyme (Roche Medical) per manufacturer protocol. Quantification of viable nucleated cell count with flow cytometry. Addition of pellet of viable nucleated cells to tSVF.
Blending of tSVF/cSVF emulsion with PRP at a 3:1 ratio. Endovaginal ultrasound guided intra-ovarian placement into ovary, preferably both if accessible.
Intervention:
干预措施: lipoaspiration harvest tSVF (Procedure)
ARM 3 emulsified tSVF and PRP, enriched with cSVF
Blood draw, processing of PRP, white blood cell poor, high platelet multiple >/= 4, e.g. Emcyte PRP tSVF preparation: Lipoaspiration utilizing closed microcannula harvesting of small volume (Tulip tumescent fluid infiltrator and Tulip Harvester). Decanting of free lipid. Emulsification of adipose tissue (Tulip Nanofat device).
cSVF preparation: lipoaspiration as above. Isolation and Concentration of cellular stromal vascular fraction (cSVF) using a Healeon Medical CentriCyte 1000 centrifuge, incubator and shaker plate with sterile Liberase enzyme (Roche Medical) per manufacturer protocol. Quantification of viable nucleated cell count with flow cytometry. Addition of pellet of viable nucleated cells to tSVF.
Blending of tSVF/cSVF emulsion with PRP at a 3:1 ratio. Endovaginal ultrasound guided intra-ovarian placement into ovary, preferably both if accessible.
Intervention:
干预措施: Platelet Rich Plasma (Procedure)
ARM 3 emulsified tSVF and PRP, enriched with cSVF
Blood draw, processing of PRP, white blood cell poor, high platelet multiple >/= 4, e.g. Emcyte PRP tSVF preparation: Lipoaspiration utilizing closed microcannula harvesting of small volume (Tulip tumescent fluid infiltrator and Tulip Harvester). Decanting of free lipid. Emulsification of adipose tissue (Tulip Nanofat device).
cSVF preparation: lipoaspiration as above. Isolation and Concentration of cellular stromal vascular fraction (cSVF) using a Healeon Medical CentriCyte 1000 centrifuge, incubator and shaker plate with sterile Liberase enzyme (Roche Medical) per manufacturer protocol. Quantification of viable nucleated cell count with flow cytometry. Addition of pellet of viable nucleated cells to tSVF.
Blending of tSVF/cSVF emulsion with PRP at a 3:1 ratio. Endovaginal ultrasound guided intra-ovarian placement into ovary, preferably both if accessible.
Intervention:
干预措施: Endovaginal Ultrasound (Procedure)
结局指标
主要结局
Patient Safety For Procedure
时间窗: 30 days
Reporting of all Adverse Events, Severe Adverse Events
次要结局
- Ovarian Morphology(Baseline, 6 month, 12 month, 18 month)
- Bone Density and Body Composition(Baseline, 12 and/or 18 months)
- Menstrual Resumption(baseline through 18 months)
- Hormonal Response(Baseline, 3 months, 6 months, 12 months, 18 months)
研究者
研究点 (1)
标识符
- NCT 编号
- NCT04444245
- 其他研究编号
- OVARIAN REJUV
日期
- 首次提交
- (6年前)
- 首次发布
- (6年前)
- 主要完成日期
- (2年前)
- 研究完成日期
- (去年)
- 最近核实
- 最近更新
- (4年前)
监管与共享
- FDA 监管药物
- 是
- 个体参与者数据共享计划
- 否
- 是否有结果
- 否