Trial Summary
What is the purpose of this trial?This trial involves giving kisspeptin and another hormone to people with PCOS to see how it affects their hormone levels. The goal is to understand if kisspeptin can help regulate their reproductive hormones. Kisspeptin has recently emerged as a key regulator of the reproductive system in women and has been shown to stimulate the secretion of another important hormone.
Is the drug Kisspeptin a promising treatment for Polycystic Ovary Syndrome (PCOS)?Yes, Kisspeptin is a promising drug for treating PCOS. It helps regulate important hormones involved in reproduction, which are often imbalanced in women with PCOS. By improving the release of these hormones, Kisspeptin could help manage symptoms like irregular menstrual cycles and fertility issues.6891113
What safety data exists for Kisspeptin treatment in PCOS?Kisspeptin and its analogs have been studied for their role in stimulating GnRH secretion, which is crucial for reproductive health. They have shown promise in treating reproductive disorders, including PCOS, by reducing androgen levels and improving reproductive function. Kisspeptin-based treatments are considered to have a favorable safety profile, with reduced risks of complications like ovarian hyperstimulation syndrome compared to traditional treatments. However, detailed safety evaluations are ongoing, and more data is needed to fully establish their safety in various clinical settings.123710
What data supports the idea that Kisspeptin for Polycystic Ovary Syndrome is an effective treatment?The available research shows that a specific form of Kisspeptin, called MVT-602, has potential as a treatment for Polycystic Ovary Syndrome (PCOS). In studies, MVT-602 was shown to increase the levels of a hormone called luteinizing hormone (LH) in women with PCOS, similar to its effects in healthy women. This suggests that MVT-602 can help regulate hormone levels in women with PCOS, which is important for managing the condition. Additionally, the research indicates that MVT-602 has a longer-lasting effect compared to another form of Kisspeptin, KP54, which could make it a more effective option for treatment.2451213
Do I have to stop taking my current medications for this trial?Yes, if you are using hormonal medications or any medication that can affect the reproductive system, you must stop taking them and complete a washout period before participating.
Eligibility Criteria
This trial is for women aged 18-45 with a BMI between 18.5 and 35 who have been diagnosed with PCOS. Participants should have normal blood pressure, not be pregnant or breastfeeding, avoid heavy alcohol use, and not be on hormonal medications unless they can stop them before the study.Treatment Details
The study aims to understand how kisspeptin affects hormone patterns in those with PCOS by comparing it to GnRH (a natural hormone). It will look at the body's response to kisspeptin and its effect on luteinizing hormone levels.
1Treatment groups
Experimental Treatment
Group I: kisspeptinExperimental Treatment1 Intervention
IV administration of kisspeptin 112-121; 24-hour infusion, up to 2 boluses.
GnRH is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Gonadorelin for:
- Infertility
- Precocious puberty
- Endometriosis
- Prostate cancer
🇪🇺 Approved in European Union as Gonadorelin for:
- Infertility
- Precocious puberty
- Endometriosis
- Prostate cancer
- Breast cancer
🇨🇦 Approved in Canada as Gonadorelin for:
- Infertility
- Precocious puberty
- Endometriosis
- Prostate cancer
Find a clinic near you
Research locations nearbySelect from list below to view details:
Massachusetts General HospitalBoston, MA
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Who is running the clinical trial?
Stephanie B. Seminara, MDLead Sponsor
References
Clinical aspects of LHRH analogues in gynaecology: a review. [2013]LHRH agonists are synthetic peptide analogues of hypothalamic luteinizing hormone releasing hormone (LHRH) with superior potency and longer duration of gonadotrophin release. Paradoxically, repeated administration causes pituitary desensitization with diminished gonadotrophin and oestradiol secretion. A state of hypogonadotrophic hypogonadism is reversibly induced; plasma oestrogen can be reduced to castrate levels. LHRH agonists reliably induce anovulation but are unlikely to replace existing contraceptive methods in most normal women. By contrast these agents offer, for the first time, the prospect of inducing a reversible pseudomenopause essentially free of side-effects. LHRH analogues promise to have a profound impact upon the management of a diverse range of oestrogen-dependent gynaecological diseases both benign and malignant. In particular, they may shortly become the gynaecological treatment of choice in endometriosis, as well as becoming part of the management of common gynaecological disorders such as dysfunctional uterine bleeding and uterine fibroids.
NIH conference. Therapeutic applications of luteinizing-hormone-releasing hormone and its analogs. [2019]The chemical structure of luteinizing-hormone-releasing hormone (LHRH) was discovered in 1971 after more than a decade of intensive effort. Subsequent physiologic studies in primates and humans showed that the biologic activity of LHRH depends on the way in which the hormone is administered. Pulsatile administration of LHRH, which mimics the natural secretory pattern, causes sustained secretion of the gonadotrophins. This method of administration has been used to induce ovulation in women with hypothalamic amenorrhea and to induce puberty and spermatogenesis in men with hypogonadotrophic hypogonadism. Continuous infusion, however, produces only transient stimulation of gonadotrophin secretion, followed by a "desensitization" response in which gonadotrophin secretion is inhibited. Thus, LHRH can either augment or inhibit gonadotrophin secretion depending on the mode of administration. Recently, long-acting synthetic analogs of LHRH have been shown to desensitize the pituitary gland and inhibit gonadotrophin release when administered as a single daily subcutaneous injection. These LHRH analogs have proved highly effective in the treatment of prostatic carcinoma and central precocious puberty. They are also being studied as a new approach to contraception and to the treatment of endometriosis and polycystic ovary syndrome.
Use of luteinizing hormone releasing hormone agonists in polycystic ovary syndrome. [2019]Luteinizing hormone releasing hormone (LHRH) agonists have been used in conjunction with gonadotrophins, and occasionally with pulsatile LHRH, for ovulation induction in women with clomiphene-citrate-resistant polycystic ovary syndrome (PCOS) and also for superovulation for in vitro fertilization (IVF) and gamete intrafallopian transfer in women with PCOS. In IVF, LHRH agonists given by the 'long protocol' before gonadotrophins are commenced have consistently shown higher pregnancy rates and higher live birth rates. Although the optimal time to commence LHRH agonist is not clearly determined, commencement in the early follicular phase possibly with pre-treatment with the combined oral contraceptive pill would avoid the risk of inadvertent administration during early pregnancy. The role of LHRH agonists in ovulation induction is less clear cut, although there may be some advantages in patients with refractory PCOS. The role of LHRH agonists in ovarian hyperstimulation syndrome and recurrent miscarriage is also discussed.
Plasma metastin levels are negatively correlated with insulin resistance and free androgens in women with polycystic ovary syndrome. [2022]This study was designed to: [1] measure, for the first time, metastin (kisspeptin) levels in women with polycystic ovary syndrome (PCOS), a condition associated with hypersecretion of LH and hyperandrogenemia; and [2] investigate the possible correlations between metastin and PCOS-related reproductive and metabolic disturbances.
Establishment and clinical application of enzyme immunoassays for determination of luteinizing hormone releasing hormone and metastin. [2011]Metastin, a 54-residue peptide, was identified as the cognate ligand of human G-protein-coupled receptor GPR54. Since metastin is a gene product of the human metastasis suppressor gene 'KiSS-1', early studies on metastin were focused on its activity as a tumor metastasis suppressor. Recently, there have been some reports that metastin is found in human plasma and is particularly abundant in the plasma of pregnant women. Dysfunction of the GPR54 receptor causes diseases that are characterized by an insufficient release of gonadotropin and lack or delay of pubertal maturation. This information strongly suggests that metastin is involved in the regulation of reproductive endocrine functions. In order to determine the plasma levels of metastin and luteinizing hormone releasing hormone (LHRH) in an isolated hypogonadotropic hypogonadism (IHH) patient, who received intermittent administrations of LHRH, we tried to establish a sensitive and specific enzyme immunoassay. The plasma LHRH levels of the patient were very high, while plasma metastin levels were at almost the same levels as circadian rhythms of healthy male humans. In the central nervous system, metastin stimulates the neuroendocrine reproductive axis. However, the effects of peripheral metastin are not known. Our result suggested that peripheral metastin had a genesis and activity different from central metastin.
Comprehensive Review on Kisspeptin and Its Role in Reproductive Disorders. [2022]Kisspeptin has recently emerged as a key regulator of the mammalian reproductive axis. It is known that kisspeptin, acting centrally via the kisspeptin receptor, stimulates secretion of gonadotrophin releasing hormone (GnRH). Loss of kisspeptin signaling causes hypogonadotrophic hypogonadism in humans and other mammals. Kisspeptin interacts with other neuropeptides such as neurokinin B and dynorphin, to regulate GnRH pulse generation. In addition, a growing body of evidence suggests that kisspeptin signaling be regulated by nutritional status and stress. Kisspeptin may also represent a novel potential therapeutic target in the treatment of fertility disorders. Early human studies suggest that peripheral exogenous kisspeptin administration stimulates gonadotrophin release in healthy adults and in patients with certain forms of infertility. This review aims to concisely summarize what is known about kisspeptin as a regulator of reproductive function, and provide an update on recent advances within this field.
Gonadotropins and Their Analogs: Current and Potential Clinical Applications. [2022]The gonadotropin receptors LH receptor and FSH receptor play a central role in governing reproductive competency/fertility. Gonadotropin hormone analogs have been used clinically for decades in assisted reproductive therapies and in the treatment of various infertility disorders. Though these treatments are effective, the clinical protocols demand multiple injections, and the hormone preparations can lack uniformity and stability. The past two decades have seen a drive to develop chimeric and modified peptide analogs with more desirable pharmacokinetic profiles, with some displaying clinical efficacy, such as corifollitropin alfa, which is now in clinical use. More recently, low-molecular-weight, orally active molecules with activity at gonadotropin receptors have been developed. Some have excellent characteristics in animals and in human studies but have not reached the market-largely as a result of acquisitions by large pharma. Nonetheless, such molecules have the potential to mitigate risks currently associated with gonadotropin-based fertility treatments, such as ovarian hyperstimulation syndrome and the demands of injection-based therapies. There is also scope for novel use beyond the current remit of gonadotropin analogs in fertility treatments, including application as novel contraceptives; in the treatment of polycystic ovary syndrome; in the restoration of function to inactivating mutations of gonadotropin receptors; in the treatment of ovarian and prostate cancers; and in the prevention of bone loss and weight gain in postmenopausal women. Here we review the properties and clinical application of current gonadotropin preparations and their analogs, as well as the development of novel orally active, small-molecule nonpeptide analogs.
Polycystic ovary syndrome (PCOS) and kisspeptin - A Sri Lankan study. [2020]Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder affecting young women. Kisspeptins are a family of closely related peptides encoded by Kiss1 gene that controls the hypothalamic-pituitary-gonadal axis by binding to its receptor (GPR54) expressed in gonadotropin-releasing hormone (GnRH) neurons and releases GnRH. Since GnRH secretion is deregulated in PCOS, we hypothesized that dysregulated gonadotropin secretion in PCOS is reflected by kisspeptin levels.
Kisspeptin and Polycystic Ovary Syndrome. [2023]Although the pathogenesis of Polycystic Ovary Syndrome (PCOS) is still unclear, the disturbance of hypothalamic-pituitary-gonadal (HPG) axis is suspected to be the main culprit in the development of PCOS. Kisspeptin, a hypothalamic peptide encoded by the KISS1 gene, is widely reported as a key factor in the regulation of luteinizing hormone (LH)/ follicular-stimulating hormone (FSH) secretion, which may be potentially involved with the development of PCOS. Objective: The objective of this study is to summarize the existing knowledge in the literature in terms of the circulating kisspeptin concentration in PCOS women, kisspeptin and metabolic profiles in PCOS women and kisspeptin expression in PCOS animal models. Method: A systematic literature search was conducted using "Pubmed," "Embase," "Web of Science" for all English language articles published up to July 2018 with the terms "PCOS," "Stein-Leventhal Syndrome," "Polycystic ovary syndrome," "metastins" and "kisspeptin". Conclusion: Overall, kisspeptin levels are higher in the PCOS population, which supports the hypothesis that an over-active KISS1 system leads to enhanced HPG-axis activity, thereby causing irregular menstrual cycles and excessive androgen release in PCOS women.
Clinical Translational Studies of Kisspeptin and Neurokinin B. [2021]Kisspeptin and neurokinin B (NKB) are hypothalamic neuropeptides that are vital for reproductive health. An absence of either kisspeptin or NKB signaling results in hypogonadotrophic hypogonadism and a failure to proceed through puberty. In recent years, several studies have demonstrated potential avenues for the clinical utility of medications that act through these pathways in the assessment and treatment of reproductive disorders. Kisspeptin acts to stimulate hypothalamic gonadotrophic-releasing hormone (GnRH) secretion from the hypothalamus. Kisspeptin induces gonadotrophin secretion in both healthy men and women, and in women with reproductive disorders such as hypothalamic amenorrhea (HA). Kisspeptin-based treatments hold promise for use during in vitro fertilization (IVF) treatment; a bolus of kisspeptin-54 induces an LH surge of 12 to 14 hours of duration sufficient to induce oocyte maturation, but with markedly reduced rates of the most significant complication of IVF treatment, ovarian hyperstimulation syndrome (OHSS). Kisspeptin could also be used chronically to restore reproductive health in patients with functional hypogonadism, such as those with HA. Furthermore, kisspeptin has potential as a diagnostic test of hypothalamic function; a "kisspeptin test" could be used in children with delayed puberty to identify the subset with genetically determined deficits in hypothalamic pathways (congenital hypogonadotrophic hypogonadism [CHH]). In addition to its role in hypothalamic GnRH pulse generation, NKB plays a critical role in the occurrence of one of the most troubling symptoms of the menopause, the "hot flush." Neurokinin-3 receptor (NK3R) antagonists are highly effective as treatments for hot flushes in postmenopausal women, with several compounds now in late-phase development. Furthermore, NK3R antagonism leads to a reduction in LH secretion by reducing GnRH pulsatility in the hypothalamus and has been shown to reduce androgen levels in women with polycystic ovary syndrome (PCOS) (in whom GnRH pulsatility is often increased). In summary, although further detailed evaluation in several clinical settings is ongoing, medications based on kisspeptin and NKB pathways have prodigious potential in the assessment and treatment of reproductive disorders.
The Correlation between Hormonal Disturbance in PCOS Women and Serum Level of Kisspeptin. [2022]Kisspeptin is a neuropeptide that upregulates gonadotropin-releasing hormone (GnRH) secretion. It is an essential element for the luteinizing hormone (LH) surge and ovulation. Women with polycystic ovary syndrome (PCOS) expose alteration in both GnRH and LH secretion levels.
Kisspeptin receptor agonist has therapeutic potential for female reproductive disorders. [2022]BACKGROUNDKisspeptin is a key regulator of hypothalamic gonadotropin-releasing hormone (GnRH) neurons and is essential for reproductive health. A specific kisspeptin receptor (KISS1R) agonist could significantly expand the potential clinical utility of therapeutics targeting the kisspeptin pathway. Herein, we investigate the effects of a KISS1R agonist, MVT-602, in healthy women and in women with reproductive disorders.METHODSWe conducted in vivo and in vitro studies to characterize the action of MVT-602 in comparison with native kisspeptin-54 (KP54). We determined the pharmacokinetic and pharmacodynamic properties of MVT-602 (doses 0.01 and 0.03 nmol/kg) versus KP54 (9.6 nmol/kg) in the follicular phase of healthy women (n = 9), and in women with polycystic ovary syndrome (PCOS; n = 6) or hypothalamic amenorrhea (HA; n = 6). Further, we investigated their effects on KISS1R-mediated inositol monophosphate (IP1) and Ca2+ signaling in cell lines and on action potential firing of GnRH neurons in brain slices.RESULTSIn healthy women, the amplitude of luteinizing hormone (LH) rise was similar to that after KP54, but peaked later (21.4 vs. 4.7 hours; P = 0.0002), with correspondingly increased AUC of LH exposure (169.0 vs. 38.5 IU∙h/L; P = 0.0058). LH increases following MVT-602 were similar in PCOS and healthy women, but advanced in HA (P = 0.004). In keeping with the clinical data, MVT-602 induced more potent signaling of KISS1R-mediated IP1 accumulation and a longer duration of GnRH neuron firing than KP54 (115 vs. 55 minutes; P = 0.0012).CONCLUSIONTaken together, these clinical and mechanistic data identify MVT-602 as having considerable therapeutic potential for the treatment of female reproductive disorders.TRIAL REGISTRATIONInternational Standard Randomised Controlled Trial Number (ISRCTN) Registry, ISRCTN21681316.FUNDINGNational Institute for Health Research and NIH.
Kisspeptin Variations in Patients with Polycystic Ovary Syndrome-A Prospective Case Control Study. [2022]Background and objectives: Kisspeptin, also named metastin, showed important roles in initiating the secretion of gonadotropin-releasing hormone (GnRH) and is an essential factor in the development of polycystic ovaries syndrome (PCOS). Several research studies noticed associations between kisspeptin levels and patients with anovulatory cycles due to PCOS with an increased LH/FSH ratio. The aim of our study was to bring scientific evidence regarding the correlation between high kisspeptin and luteinizing hormone values in subfertile women due to PCOS. Materials and Methods: A prospective case-control study was conducted in "Elena Doamna" Hospital of Obstetrics and Gynecology between 4 January 2021 and 1 March 2022. All patients agreed to participate in our study, had ages between 18 and 45 years old, and had a body mass index between 18.5 and 30 kg/m2. The study group consisted of subfertile patients with PCOS and menstrual disturbances, including amenorrhea or oligomenorrhea. The control group consisted of healthy patients with ovulatory cycles and no other reproductive or endocrinology pathologies. During the follicular phase of their menstrual cycle, patients had blood samples taken with the dosage of kisspeptin, LH, FSH, estradiol, insulin, glycemic levels, testosterone, and prolactin. Pelvic ultrasounds and clinical examinations were performed as well. Results: Significant differences were observed in kisspeptin, LH, FSH, and estradiol levels between patients with PCOS and the control group. After the univariate analysis, PCOS was significantly associated with increased kisspeptin, increased LH, and decreased FSH. There was no significant association between PCOS, estradiol, prolactin, and insulin. Conclusions: kisspeptin serum values are higher in subfertile PCOS patients, supporting the hypothesis that an over-stimulation of the KISS1 system might cause the hyper-stimulation of the HPG-axis.