Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Uterine Cervical Dysplasia

Squamous Intraepithelial Lesions of the Cervix

Carcinoma

Carcinoma, Squamous Cell

Carcinoma in Situ

Precancerous Conditions

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Cervical Intraepithelial Neoplasia

Participants received three IM injections of 6 milligram (mg) (in 1 milliliter \[mL\]) VGX-3100 followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12.

Participants received three IM injections of 1 mL VGX-3100 matching placebo followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12.

1 mL VGX-3100 will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.

VGX-3100

1 mL of Placebo will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.

Placebo

Intramuscular injection followed by EP with the CELLECTRA™ 5PSP device.

Electroporation (EP)

Jeffrey Skolnik, MD

HPV-301 is a prospective, randomized, double-blind, placebo controlled Phase 3 study to determine the efficacy, safety, and tolerability of VGX-3100 administered by intramuscular (IM) injection followed by electroporation (EP) delivered with CELLECTRA™ 5PSP in adult women with histologically confirmed cervical high grade squamous intraepithelial lesion (HSIL) (cervical intraepithelial neoplasia grade 2 \[CIN2\] or grade 3 \[CIN3\]) associated with human papillomavirus (HPV) 16 and/or HPV-18.

REVEAL 1 (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)

A Prospective, Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of VGX-3100 Delivered Intramuscularly Followed by Electroporation With CELLECTRA™-5PSP for the Treatment of HPV-16 and/or HPV-18 Related High Grade Squamous Intraepithelial Lesion (HSIL) of the Cervix

Participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL, no evidence of HPV-16 and/or HPV-18 at the Week 36 time frame, and participants in which excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined by histology as negative, squamous atypia, or low-grade intraepithelial lesion (LSIL). Cervical samples for HPV-16 and/or HPV-18 were collected using the ThinPrep®.

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. An SAE is any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.

Participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL at Week 36 and participants in which an excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined by histology as negative, squamous atypia, or LSIL.

Participants with no evidence of HPV-16 and/or HPV-18 at the Week 36 time frame and participants in which an excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. Cervical samples for HPV-16 and/or HPV-18 were collected using the ThinPrep®.

Participants with no histologic evidence of cervical HSIL, squamous atypia, or LSIL at the Week 36 time frame and participants in which an excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined as no evidence of cervical squamous intraepithelial neoplasia 1 (CIN1), CIN2, or CIN3 on biopsies or excisional treatment.

Participants with no histologic evidence of cervical HSIL, squamous atypia, and LSIL, no evidence of HPV-16 and/or HPV-18 by type specific HPV testing at the Week 36 time, and participants in which an excision or biopsy sample was not obtained between initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined as no evidence of CIN1, CIN2, or CIN3 on biopsies or excisional treatment.

Participants with no histologic evidence of cervical Adenocarcinoma in situ or cervical carcinoma at the Week 36 timeframe relative to baseline and participants in which an excision or biopsy sample was not obtained between initial dose up to Week 36 were considered as responders.

Participants with no evidence of HPV-16 and/or HPV-18 on specimens from noncervical anatomic locations (oropharynx, vagina and intra-anal) at the Week 36 time frame were considered as responder.

A standardized binding enzyme-linked immunosorbent assay (ELISA) was performed to measure the anti-HPV-16/18 antibody response induced by VGX-3100.

Assessment of cellular immune activity occurred via the application of the Interferon-γ enzyme-linked immunosorbent spot (IFN-γ ELISpot). Peripheral blood mononuclear cells (PBMCs) isolated from whole blood sample were used for analysis.

Assessment of cellular immune activity was measured using the application flow cytometry for the purposes of performing a Lytic Granule Loading Assay. The Lytic Granule Loading assay examines the following external cellular markers: CD3, CD4, CD8 (T cell identification), CD137, CD38 and CD69 (T cell activation markers) as well as PD-1 (exhaustion/activation marker). Here change from baseline in CD8+CD137+Perforin+, CD8+CD38+Perforin+ and CD8+CD69+Perforin+ are reported.

Inovio Pharmaceuticals

Safety set included all participants who received at least one dose of clinical trial treatment. One participant received mixed treatment and was excluded from the safety analysis.

Participants received three IM injections of 6 mg (in 1 mL) VGX-3100 followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12.

VGX-3100 + Electroporation (EP)

Placebo + EP

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

American Indian or Alaska Native

Asian

Black or African American

Native Hawaiian or Other Pacific Islander

White

Other

Multiple

Missing

Race/Ethnicity, Customized

ITT population included all participants who were randomized.

Study Director

Percentage of Participants With No Evidence of Cervical HSIL on Histology and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples

Number of Participants with any AE

Number of Participants with any SAE

Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Investigational Treatment for the Duration of the Study

Percentage of Participants With No Evidence of Cervical HSIL on Histology

Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing

Percentage of Participants With No Evidence of LSIL or HSIL on Histology

Percentage of Participants With No Evidence of LSIL or HSIL and No Evidence of HPV-16 and/or HPV-18

Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma

Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations

HPV-16 E7 at Week 15

HPV-16 E7 at Week 36

HPV-18 E7 at Week 15

HPV-18 E7 at Week 36

mITT population included all participants who received at least one dose of clinical trial treatment and who had the analysis endpoint of interest. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints.

Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations

HPV-16 E6: Baseline

HPV-16 E6: Change from Baseline at Week 15

HPV-16 E6: Change from Baseline at Week 36

HPV-16 E7: Baseline

HPV-16 E7: Change from Baseline at Week 15

HPV-16 E7: Change from Baseline at Week 36

HPV-18 E6: Baseline

HPV-18 E6: Change from Baseline at Week 15

HPV-18 E6: Change from Baseline at Week 36

HPV-18 E7: Baseline

HPV-18 E7: Change from Baseline at Week 15

HPV-18 E7: Change from Baseline at Week 36

Change From Baseline in Interferon-Gamma Response Magnitude

CD8+CD137+Perforin+: Baseline

CD8+CD137+Perforin+: Change from Baseline at Week 15

CD8+CD38+Perforin+: Baseline

CD8+CD38+Perforin+: Change from Baseline at Week 15

CD8+CD69+Perforin+: Baseline

CD8+CD69+Perforin+: Change from Baseline at Week 15

Change From Baseline in Flow Cytometry Response Magnitude

Overall Study

Infections

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Uterine Cervical Neoplasms

Vaginal Neoplasms

Vulvar Neoplasms

Warts

Condylomata Acuminata

Genital Neoplasms, Female

Urogenital Neoplasms

Vulvar Diseases

Vaginal Diseases

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Communicable Diseases

Papillomavirus Infections

Virus Diseases

DNA Virus Infections

Skin Diseases

Skin Diseases, Viral

Tumor Virus Infections

Skin Diseases, Infectious

Vaginal Cancer

Vulvar Cancer

All Drugs and Chemicals

Vaccines

Subjects received 3 doses of 9-valent HPV vaccine according to a 0, 2, 6-month schedule.

9-valent HPV Recombinant Vaccine

Subjects received 3 doses of Placebo according to a 0, 2, 6-month schedule.

To evaluate the safety and immunogenicity of the 9-valent Human Papillomavirus (Types 6, 11, 16, 18,31,33,45,52 and 58) Recombinant Vaccine (Hansenula Polymorpha) in Chinese Female Subjects Aged 9-45 Years.

Evaluate the Safety and Primary Immunogenicity of 9-valent HPV Recombinant Vaccine in Chinese Healthy Females

A Randomized, Double-Blind and Placebo-Controlled Phase I Study to Evaluate the Safety and Primary Immunogenicity of the 9-valent Human Papillomavirus (Types 6, 11, 16, 18,31,33,45,52 and 58) Recombinant Vaccine (Hansenula Polymorpha) in Chinese Female Subjects Aged 9-45 Years

Chongqing Bovax Biopharmaceutical Co., Ltd.

Shanghai Bovax Biotechnology Co., Ltd.

Sexually active young women aged 12 to 22 years of age without a previous history of CIN. Women are not eligible for entry if pregnant or known immunosuppression.

Anna-Barbara Moscicki, MD

The natural history of human papillomavirus (HPV) is most likely influenced by both innate and adaptive mucosal immunity. More specifically, we hypothesize that Toll like receptors (TLR) play an important role in cervical innate immunity to HPV through secretions of proinflammatory, chemotactic and anti-viral cytokines. Up-regulated TLR expression will also result in activation of dendritic cells and T cells that in turn will promote a T helper (Th) l like response through secretion of several cytokines and consequently, the induction of a successful cell mediated immune (CMI) response.

The natural history of HPV is most likely influenced by both innate and adaptive mucosal immunity. More specifically, we hypothesize that Toll like receptors (TLRs) play an important role in cervical innate immunity to HPV through secretions of proinflammatory, chemotactic and anti-viral cytokines. Up-regulated TLR expression will also result in activation of dendritic cells and T cells that in turn will promote a Thl like response through secretion of several cytokines and consequently, the induction of a successful cell mediated immune (CMI) response.

We propose to: 1) examine, in cervical cell samples, the association among TRL expression, TRL-associated cytokines that mediate innate immunity and clearance of incident HPV infection; 2) examine, in cervical cell samples, the association among TRL expression, TRL-associated cytokines that induce and mediate adaptive immunity and HPV clearance; and 3) examine the association among TLR induced Th-1 responses measured in cervical cell samples, HPV specific CMI responses detected in peripheral blood (PB) and HPV clearance. Adolescent and young women who were a) entered into the cohort during the initial 1990-1995 period and have continued to be followed and b) entered into the cohort during the last recruitment wave (2000-2005) will be asked to continue followup for an additional five years (2005-2010). These women will have been well characterized at the time of the initiation of this study with HPV at their entry visit and 4-month interval sampling for HPV DNA, cytology, bacterial vaginosis, colpophotographs (assessment of cervical maturation), C. trachomatis and N. gonorrhea testing, cervical cell cytokines by reverse transcriptase polymerase chain reaction (RT-PCR) and peripheral blood (PB) CMI for HPV 16 positive women. Women will be continued to be characterized for the above at the same intervals through-out the follow-up. Measures of innate and adaptive immunity by RT PCR using cervical cells and by Luminex technology have been added to the same 4 month interval testing as HPV DNA, cytology and other cervical cytokines described. Women positive for HPV 16 will get additional blood for CMI using Interferon (IFN)-y Enzyme linked immunospot (EliSpot) technique for detection of anti-E6 and E7 responses. We also examine the natural history of anal HPV in these women. We acknowledge that this design simplifies the pleiotropic nature of cytokines. However, we feel that this model reflects plausible mechanisms involved in HPV control and is feasible to test in our cohort. Information garnered from this type of study will be critical in developing vaccine strategies and therapies as well as illuminating immune responses developed in the mucosal epithelium.

Rbc, WBC vaginal lavages ,cytology,saliva ,anal samples

Natural History of HPV From Infection to Neoplasia in Adolescents and Young Women

Natural History of Human Papillomavirus From Infection to Neoplasia in Adolescents and Young Women - Effect of Tobacco on Cervical Neoplasia in Young Women

National Institutes of Health (NIH)

National Cancer Institute (NCI)

University of California, Los Angeles

Disease Attributes

9-valent HPV recombinant vaccine (Hansenula Polymorpha) All subjects aged 9 to 45 years received 3 doses of 9v HPV vaccine at 0,2,6 month scehdule

9-valent HPV vaccine

Huakun Lv

Person(s) responsible for the overall scientific leadership of Lv

This phase 3 study will evaluate the immunogenicity and safety of 9-valent HPV recombinant vaccine in Chinese females aged 9 to 45 years

This study (protocol 9-HPV-3003) is an immunogenicity and safety study in the subjects (9-19 years of age) who received the 9-valent HPV recombinant vaccine compared with the subjects (20-45 years of age). In this study, we will assess whether the immunogenicity of the 9-valent HPV vaccine given 3-dose schedule in the subjects (9-19 years of age) in noninferior to that in the subjects (20-45 years of age) receiving 3 doses, while assessing the safety of this vaccine.

Immunobridging Study of 9-valent Human Papillomavirus Recombinant Vaccine in Chinese Females Aged 9 to 19 Years

Evaluating the Immunogenicity and Safety of 9-valent Human Papillomavirus(Type6, 11, 16, 18, 31, 33, 45, 52 and 58) Recombinant Vaccine in Chinese Females Aged 9 to 45 Years: A Phase 3, Open-label, Non-randomised Clinical Trial

Adverse events reported within 30 minutes after each dose

Solicited adverse events reported between day 0 to day 7 after each dose

Unsolicited adverse events reported between day 0 to day 30 after each dose

Serious adverse events reported during the study period

Pregnant event and pregnant outcome reported during the study period

The primary outcome measure for assessing vaccine immunogenicity, among subjects aged between 9 and 45, is the results of seroconversion rate of neutralizing antibodies after immunization in pre-immune negative subjects from 30 days after the last dose (3 doses schedule, Month 7) to HPV 6, 11, 16, 18, 31, 33, 45, 52 , and 58.

The secondary outcome measure for assessing vaccine immunogenicity, among subjects aged between 9 and 45, is the geometric mean titer (GMT) from 30 days after the last dose (3 doses schedule, Month 7) to HPV 6, 11, 16, 18, 31, 33, 45, 52 , and 58.

To assess vaccine immunogenicity among the subjects aged between 9 and 26, is the seroconversion rate of neutralizing antibodies and the GMT from 30 days after the last dose (3 doses schedule, Month 7) to HPV 6, 11, 16, 18, 31, 33, 45, 52 , and 58.

After receiving all 3 doses vaccinations, the subjects aged 9 to 19 years will be followed for 60 month (Month 12/24/36/48/60) after first vaccination to assess the GMT and seropositive rate (4-fold-increase) to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58.

Immune System Diseases

Acquired Immunodeficiency Syndrome

HIV Infections

HIV Seropositivity

Blood-Borne Infections

Lentivirus Infections

Retroviridae Infections

RNA Virus Infections

Syndrome

Immunologic Deficiency Syndromes

Anti-Arrhythmia Agents

Channel Blockers

Central Nervous System Depressants

Analgesics

Lidocaine

Nitrous Oxide

LEEP treatment of CIN 2/3 cervical lesion in HIV positive women (standard of Care)

Cryotherapy treatment of CIN 2/3 cervical lesions

This is involves freezing the lesions with a cryo gun using Nitrous Oxide for 3 minutes-- wait 5 minutes and then refreezing for 3 more minutes. This procedure uses the Wallach cryogun

Cryotherapy

The cervix is anaesthetized with lidocaine and then a electric loop is applied to the cervical lesion which is cut with one pass. The LEEP machine used is the automatic Finesse Machine.

LEEP

Cynthia S Firnhaber, MD

To compare the efficacy of cryotherapy and large loop excision of the transformation zone (LLETZ) procedures for the treatment of high-grade cervical intra-epithelial neoplasia (CIN2/3) among HIV-seropositive women by follow-up VIA, cytology and Human Papillomavirus.

Hypothesis: LEEP will be more effective than cryotherapy in removing CIN 2/3 lesions in HIV positive women in South Africa

Cervical cancer is the most common cancer in HIV positive women. This is due to immunosuppression and lack of organized and effective screening and treatment programs in Africa. Other screening and treatment modalities need to be evaluated in resource limited countries as there is not capacity in most of these countries to implement a cytology/histology based program. The treatment modality of cryotherapy is easy to train and perform and can be done by a nurse. LEEP requires significant training usually doctors and skills in administering local anaesthetic. This study compares the two modalities of cryotherapy vs LEEP in a randomized controlled study in HIV positive women in South Africa.

A. PRIMARY AIMS (S.A.):

1. To compare the efficacy of cryotherapy and large loop excision of the transformation zone (LLETZ) procedures for the treatment of high-grade cervical intra-epithelial neoplasia (CIN2/3) among HIV-seropositive women by follow-up VIA, cytology and HPV.
2. To determine the utility of subsequent HPV DNA testing as a marker of effective treatment following the treatment of CIN 2/3 among HIV-seropositive women.
3. To compare the safety of cryotherapy versus LLETZ in HIV seropositive women.

SECONDARY AIMS:

1. To describe HIV disease status (CD4, HIV viral load), demographics, and sexual behavior in each treatment arm (LLETZ and cryotherapy) in HIV seropositive women.

3. To determine the cervical disease recurrence rates with cryotherapy and LLETZ.

4. To evaluate the relationship between HIV status, demographics, HPV, and sexual behavior with the clearance of cervical disease at the ectocervical and endocervical margins in HIV seropositive women.

Validation of Implementation of Cervical Dysplasia Treatment Modalities in HIV-Seropositive Women

To compare the efficacy of cryotherapy and large loop excision of the transformation zone (LLETZ) procedures for the treatment of high-grade cervical intra-epithelial neoplasia (CIN2/3) among HIV-seropositive women by follow-up VIA, cytology and HPV.

To determine the utility of subsequent HPV DNA testing as a marker of effective treatment following the treatment of CIN 2/3 among HIV-seropositive women.

To compare the safety of cryotherapy versus LLETZ in HIV seropositive women by evaluating adverse events as measured by the Division of AIDS toxicity table 2004 (revised August 2010)

To describe HIV disease status (CD4, HIV viral load), demographics, tissue margins and sexual behavior in each treatment arm (LLETZ and cryotherapy) in HIV seropositive women.

To determine the cervical disease recurrence rates with cryotherapy and LLETZ at 6 months and 12 months by colposcopy

University of Witwatersrand, South Africa

Associate Professor of Medicine

IM injections with VGX-3100 followed by electroporation (EP) using the CELLECTRA™-5PSP device on Day 0, Week 4 and Week 12.

IM injections with matching placebo followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4 and Week 12.

1 milliLiter (mL) VGX-3100 will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.

CELLECTRA™-5PSP is used for EP following IM injection of VGX 3100 or placebo on Day 0, Week 4 and Week 12.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
REVEAL 1 (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)	NCT03185013	Cervical Dyspla... Cervical High G... HSIL	VGX-3100 Placebo Electroporation...	18 Years -	Inovio Pharmaceuticals
Evaluate the Safety and Primary Immunogenicity of 9-valent HPV Recombinant Vaccine in Chinese Healthy Females	NCT03676101	Cervical Cancer... Vulvar Cancer Vaginal Cancer CIN1 CIN2 CIN 3 AIS Invasive Carcin... Mild Dysplasia ... Moderate Dyspla... Vin III VaIN1 VaIN2 VaIN3 Genital Wart	9-valent HPV Re... Placebo	9 Years - 45 Years	Shanghai Bovax Biotechnology Co., Ltd.
Natural History of HPV From Infection to Neoplasia in Adolescents and Young Women	NCT01366742	Human Papilloma... CIN 2 CIN 3		13 Years - 22 Years	University of California, Los Angeles
REVEAL 1 (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)	NCT03185013	Cervical Dyspla... Cervical High G... HSIL	VGX-3100 Placebo Electroporation...	18 Years -	Inovio Pharmaceuticals
Immunobridging Study of 9-valent Human Papillomavirus Recombinant Vaccine in Chinese Females Aged 9 to 19 Years	NCT04895020	HPV Infections Cervical Cancer Vulvar Cancer Vaginal Cancer CIN1 CIN2 CIN 3 VaIN1 VaIN2 VaIN3 Genital Wart VIN 1 VIN 2 VIN 3 AIS	9-valent HPV va...	9 Years - 45 Years	Shanghai Bovax Biotechnology Co., Ltd.
Evaluate the Safety and Primary Immunogenicity of 9-valent HPV Recombinant Vaccine in Chinese Healthy Females	NCT03676101	Cervical Cancer... Vulvar Cancer Vaginal Cancer CIN1 CIN2 CIN 3 AIS Invasive Carcin... Mild Dysplasia ... Moderate Dyspla... Vin III VaIN1 VaIN2 VaIN3 Genital Wart	9-valent HPV Re... Placebo	9 Years - 45 Years	Shanghai Bovax Biotechnology Co., Ltd.
Natural History of HPV From Infection to Neoplasia in Adolescents and Young Women	NCT01366742	Human Papilloma... CIN 2 CIN 3		13 Years - 22 Years	University of California, Los Angeles
Validation of Implementation of Cervical Dysplasia Treatment Modalities in HIV-Seropositive Women	NCT01723956	Cervical Intrae...	Cryotherapy LEEP	18 Years - 65 Years	University of Witwatersrand, South Africa
REVEAL 2 Trial (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)	NCT03721978	Cervical Dyspla... Cervical High G... HSIL	VGX-3100 Placebo CELLECTRA™-5PSP	18 Years -	Inovio Pharmaceuticals

Spots Global Cancer Trial Database for cin 3

Every month we try and update this database with for cin 3 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cin 3

Every month we try and update this database with for cin 3 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cin 3 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.