Ignite Creation Date:
2025-12-25 @ 2:13 AM
Ignite Modification Date:
2026-02-25 @ 11:03 PM
Study NCT ID:
NCT03337360
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-04-04
First Post:
2017-11-06
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Impact of a Nutritional Supplement (Impryl®) on Male Fertility
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D007248', 'term': 'Infertility, Male'}], 'ancestors': [{'id': 'D005832', 'term': 'Genital Diseases, Male'}, {'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D007246', 'term': 'Infertility'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2020-05-19', 'size': 841491, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_001.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2020-05-29T04:06', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Multicentre, randomised double blind placebo controlled clinical trial/superiority study.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 1200}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2018-04-23', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-04', 'completionDateStruct': {'date': '2026-04-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-04-03', 'studyFirstSubmitDate': '2017-11-06', 'studyFirstSubmitQcDate': '2017-11-06', 'lastUpdatePostDateStruct': {'date': '2025-04-04', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2017-11-09', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-01-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Ongoing pregnancy rate', 'timeFrame': '15 months', 'description': 'Ongoing pregnancy ≥10-12 weeks of gestation'}], 'secondaryOutcomes': [{'measure': 'Overall pregnancy rate', 'timeFrame': '15 months', 'description': 'All pregnancies confirmed with a positive pregnancy (HCG) test'}, {'measure': 'Time to pregnancy 1 - start intervention', 'timeFrame': '15 months', 'description': 'The time between start of intervention and reaching ongoing pregnancy'}, {'measure': 'Time to pregnancy 1 - start fertility treatment', 'timeFrame': '15 months', 'description': 'The time between start of fertility treatment and reaching ongoing pregnancy'}, {'measure': 'Change in semen parameters leading to change in treatment category', 'timeFrame': '15 months', 'description': 'Between baseline and 3 months intervention, based on pre-wash total motile sperm count (TMSC) from the subpopulation from Radboudumc and sites that deliver a pre-wash TMSC before IUI/IVF/ICSI'}, {'measure': 'Number of miscarriages', 'timeFrame': '15 months', 'description': 'Defined as a non-vital intra-uterine pregnancy before 16 weeks of gestation'}, {'measure': 'Live birth rate', 'timeFrame': '15 months', 'description': 'Live birth rate defined as beyond 24 weeks of gestation, the birth of a living child.'}, {'measure': 'Adverse effects', 'timeFrame': '15 months', 'description': 'Gastro-intestinal problems such as reflux, obstipation, diarrhea, nausea or vomiting, furthermore loss of appetite, headache, dizziness, pruritus or skin rash.'}, {'measure': 'Embryo fertilization rate', 'timeFrame': '15 months', 'description': 'Relative improvement. Fertilization rate is the percentage of oocytes with \\>=2 PN after insemination (IVF) of injection (ICSI).'}, {'measure': 'Embryo-utilization rate', 'timeFrame': '15 months', 'description': "Relative improvement of the embryo-utilization rate (EUR), defined as the number of high quality embryos obtained, embryo's used at transfer plus the number of embryos frozen, divided by the number of zygotes obtained in a cycle"}, {'measure': 'Live birth rate', 'timeFrame': '15 months', 'description': 'All live births'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['fertility', 'male subfertility', 'foodsupplement', 'oxidative stress'], 'conditions': ['Male Subfertility']}, 'referencesModule': {'references': [{'pmid': '1735495', 'type': 'BACKGROUND', 'citation': 'Iwasaki A, Gagnon C. Formation of reactive oxygen species in spermatozoa of infertile patients. Fertil Steril. 1992 Feb;57(2):409-16. doi: 10.1016/s0015-0282(16)54855-9.'}, {'pmid': '8359932', 'type': 'BACKGROUND', 'citation': 'Zini A, de Lamirande E, Gagnon C. Reactive oxygen species in semen of infertile patients: levels of superoxide dismutase- and catalase-like activities in seminal plasma and spermatozoa. Int J Androl. 1993 Jun;16(3):183-8. doi: 10.1111/j.1365-2605.1993.tb01177.x.'}, {'pmid': '7817460', 'type': 'BACKGROUND', 'citation': 'Shekarriz M, Thomas AJ Jr, Agarwal A. Incidence and level of seminal reactive oxygen species in normal men. Urology. 1995 Jan;45(1):103-7. doi: 10.1016/s0090-4295(95)97088-6.'}, {'pmid': '16413322', 'type': 'BACKGROUND', 'citation': 'Agarwal A, Prabakaran S, Allamaneni S. What an andrologist/urologist should know about free radicals and why. Urology. 2006 Jan;67(1):2-8. doi: 10.1016/j.urology.2005.07.012. No abstract available.'}, {'pmid': '18281241', 'type': 'BACKGROUND', 'citation': 'Tremellen K. Oxidative stress and male infertility--a clinical perspective. Hum Reprod Update. 2008 May-Jun;14(3):243-58. doi: 10.1093/humupd/dmn004. Epub 2008 Feb 14.'}, {'pmid': '25504418', 'type': 'BACKGROUND', 'citation': 'Showell MG, Mackenzie-Proctor R, Brown J, Yazdani A, Stankiewicz MT, Hart RJ. Antioxidants for male subfertility. Cochrane Database Syst Rev. 2014;(12):CD007411. doi: 10.1002/14651858.CD007411.pub3. Epub 2014 Dec 15.'}, {'pmid': '25073983', 'type': 'BACKGROUND', 'citation': 'Dattilo M, Cornet D, Amar E, Cohen M, Menezo Y. The importance of the one carbon cycle nutritional support in human male fertility: a preliminary clinical report. Reprod Biol Endocrinol. 2014 Jul 29;12:71. doi: 10.1186/1477-7827-12-71.'}, {'pmid': '27423667', 'type': 'BACKGROUND', 'citation': "Dattilo M, D'Amato G, Caroppo E, Menezo Y. Improvement of gamete quality by stimulating and feeding the endogenous antioxidant system: mechanisms, clinical results, insights on gene-environment interactions and the role of diet. J Assist Reprod Genet. 2016 Dec;33(12):1633-1648. doi: 10.1007/s10815-016-0767-4. Epub 2016 Jul 16."}, {'pmid': '40996763', 'type': 'DERIVED', 'citation': 'de Ligny WR, de Bruin JP, Smits RM, Goovaerts IGF, Peeters K, Nap AW, Boxmeer JC, Donker RB, Schoonenberg M, Koks CAM, van Rumste MME, Visser J, Gielen SCJP, Boomsma CM, Smeenk JMJ, van Oppenraaij RHF, Cox T, Janse F, Muller LT, Brink-van der Vlugt JJ, Braat DDM, Fleischer K. Antioxidant Treatment and the Chance to Conceive in Men Seeking Fertility Care: The SUMMER Randomized Clinical Trial. JAMA Netw Open. 2025 Sep 2;8(9):e2532405. doi: 10.1001/jamanetworkopen.2025.32405.'}, {'pmid': '32616489', 'type': 'DERIVED', 'citation': "Smits R, D'Hauwers K, IntHout J, Braat D, Fleischer K. Impact of a nutritional supplement (Impryl) on male fertility: study protocol of a multicentre, randomised, double-blind, placebo-controlled clinical trial (SUppleMent Male fERtility, SUMMER trial). BMJ Open. 2020 Jul 2;10(7):e035069. doi: 10.1136/bmjopen-2019-035069."}], 'seeAlsoLinks': [{'url': 'http://impryl.com/', 'label': 'Website Impryl'}]}, 'descriptionModule': {'briefSummary': 'Infertility is a worldwide problem and about 10%-15% of all couples will be affected by the inability to have children. In approximately 50% of infertile couples a male factor is involved. Male infertility is of multifactorial origin. In the past decade, the role of oxidative stress on sperm has been researched thoroughly and found to be the problem in 30% to 80% of male infertility cases.\n\nImpryl® is a nutritional supplement mainly consisting of vitamin B, which works on the metabolic system by activating the one carbon cycle and recycling of homocysteine without the use of any direct strong antioxidants.\n\nIn this study the investigators want to determine the effectiveness of nutritional supplement Impryl® in men of infertile couples on ongoing pregnancy rate, with or without assisted reproduction technology (ART).', 'detailedDescription': 'Rationale: Infertility is a worldwide problem and about 10%-15% of all couples will be affected by the inability to have children. In approximately 50% of infertile couples a male factor is involved. In the past decade, the role of oxidative stress on sperm has been researched thoroughly and found to be the problem in 30% to 80% of male infertility cases. Impryl® is a nutritional supplement which works on the metabolic system and regulation of oxidative stress by activating the 1-Carbon cycle and therefore recycling of homocysteine.\n\nObjective: To determine the effectiveness of nutritional supplement Impryl® in men of infertile couples on ongoing pregnancy rate, with or without assisted reproduction technology (ART).\n\nStudy design: Multicentre, randomised double blind placebo controlled clinical trial/superiority study.\n\nStudy population: All participants in this study are male adults, age 18-50 years, part of a couple that is diagnosed with infertility, regardless the outcome of semen analysis. The couple will either start or is already started with fertility treatment, i.e. expectative management (EM, duration 6 months), intra-uterine insemination (IUI) with or without ovarian stimulation (mild ovarian hyperstimulation (MOH) or ovulation induction (OI)), either in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment.\n\nIntervention: Impryl® or placebo, with identical appearance one tablet each day for a total duration of maximal 6 months. Patients can start directly with study medication and fertility treatment (or to conceive spontaneously).\n\nMain study parameters/endpoints: The primary outcome is the number of ongoing pregnancies confirmed by ultrasound at ≥ 10-12 weeks. Secondary outcomes are change in semen parameters between baseline and 3 months intervention in IUI/IVF/ICSI group, based on (pre-wash) total motile sperm count (TMSC), leading to a change in treatment category Furthermore the occurrence of pregnancy, time to pregnancy, embryo fertilization rate in IVF/ICSI, embryo-utilization rate in IVF/ICSI, number of miscarriages and live birth rate are documented within the study period. The occurrence of adverse events will be reported.'}, 'eligibilityModule': {'sex': 'MALE', 'stdAges': ['ADULT'], 'maximumAge': '50 Years', 'minimumAge': '18 Years', 'genderBased': True, 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\nCouples with failure to conceive for at least 12 months and starting with EM or Couples starting with 1st/ 2nd/3rd cycle of IUI (with/without ovarian stimulation) or Couples starting with 1st/ 2nd/3rd cycle of IVF/ICSI\n\nFurthermore:\n\n* Male with age 18-50 years\n* Female partner with age 18-43 years\n* Willing and able to give informed consent\n\nExclusion Criteria:\n\n* Planned or performed diagnostic testicular biopsy (TESE) or percutaneous epididymal sperm aspiration (PESA)\n* Use of donor-, cryopreserved- or electro-ejaculated semen\n* Ovulation induction (OI) without IUI\n* IVF for an absolute tubal factor\n* Embryo-transfers after cryopreservation\n* Embryo-transfer after pre-implantation genetic diagnosis\n* Known genetic abnormalities related to infertility\n* Known urological abnormality such as a varicocele or bilateral cryptorchism\n* Use of other vitamin supplements'}, 'identificationModule': {'nctId': 'NCT03337360', 'acronym': 'SUMMER', 'briefTitle': 'The Impact of a Nutritional Supplement (Impryl®) on Male Fertility', 'organization': {'class': 'OTHER', 'fullName': 'Radboud University Medical Center'}, 'officialTitle': 'The Impact of a Nutritional Supplement (Impryl®) on Male Fertility', 'orgStudyIdInfo': {'id': 'NL61414.091.17'}, 'secondaryIdInfos': [{'id': 'NTR6551', 'type': 'REGISTRY', 'domain': 'Nederlands Trial Register'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Impryl', 'description': 'One tablet daily for 6 months', 'interventionNames': ['Dietary Supplement: Impryl']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'One tablet daily for 6 months', 'interventionNames': ['Other: Placebo']}], 'interventions': [{'name': 'Impryl', 'type': 'DIETARY_SUPPLEMENT', 'description': 'Food supplement with betaine, cystine, zinc, niacin, folic acid (5MTHF-glucosamine), Vitamin B12 (cobalamin), Vitamin B6, Vitamin B2 (riboflavin)', 'armGroupLabels': ['Impryl']}, {'name': 'Placebo', 'type': 'OTHER', 'description': 'Inactive ingredients, placebo', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Voorburg', 'state': 'Gelderland', 'country': 'Netherlands', 'facility': 'Fertiliteitscentrum Voorburg'}, {'zip': '5200ME', 'city': "'s-Hertogenbosch", 'country': 'Netherlands', 'facility': 'Jeroen Bosch Ziekenhuis', 'geoPoint': {'lat': 51.69917, 'lon': 5.30417}}, {'zip': '7334DZ', 'city': 'Apeldoorn', 'country': 'Netherlands', 'facility': 'Gelre Ziekenhuizen', 'geoPoint': {'lat': 52.21, 'lon': 5.96944}}, {'zip': '6815AD', 'city': 'Arnhem', 'country': 'Netherlands', 'facility': 'Rijnstate', 'geoPoint': {'lat': 51.98, 'lon': 5.91111}}, {'zip': '5835DV', 'city': 'Boxmeer', 'country': 'Netherlands', 'facility': 'Maasziekenhuis Pantein', 'geoPoint': {'lat': 51.64667, 'lon': 5.94722}}, {'zip': '4818CK', 'city': 'Breda', 'country': 'Netherlands', 'facility': 'Amphia ziekenhuis', 'geoPoint': {'lat': 51.58656, 'lon': 4.77596}}, {'zip': '7002BL', 'city': 'Doetinchem', 'country': 'Netherlands', 'facility': 'Slingeland Ziekenhuis', 'geoPoint': {'lat': 51.965, 'lon': 6.28889}}, {'zip': '3318AT', 'city': 'Dordrecht', 'country': 'Netherlands', 'facility': 'Albert Schweitzer ziekenhuis', 'geoPoint': {'lat': 51.81, 'lon': 4.67361}}, {'zip': '5623EJ', 'city': 'Eindhoven', 'country': 'Netherlands', 'facility': 'Catharina Ziekenhuis Eindhoven', 'geoPoint': {'lat': 51.44083, 'lon': 5.47778}}, {'zip': '5424SM', 'city': 'Elsendorp', 'country': 'Netherlands', 'facility': 'Nij Geertgen', 'geoPoint': {'lat': 51.58083, 'lon': 5.76944}}, {'zip': '7824AA', 'city': 'Emmen', 'country': 'Netherlands', 'facility': 'Treant ziekenhuis Scheper', 'geoPoint': {'lat': 52.77917, 'lon': 6.90694}}, {'zip': '4207HG', 'city': 'Gorinchem', 'country': 'Netherlands', 'facility': 'Nij Linge', 'geoPoint': {'lat': 51.83652, 'lon': 4.97243}}, {'city': 'Leiderdorp', 'country': 'Netherlands', 'facility': 'Medisch Centrum Kinderwens', 'geoPoint': {'lat': 52.15833, 'lon': 4.52917}}, {'zip': '6500HB', 'city': 'Nijmegen', 'country': 'Netherlands', 'facility': 'Radboudumc', 'geoPoint': {'lat': 51.8425, 'lon': 5.85278}}, {'zip': '4708AE', 'city': 'Roosendaal', 'country': 'Netherlands', 'facility': 'Bravis Ziekenhuis', 'geoPoint': {'lat': 51.53083, 'lon': 4.46528}}, {'zip': '3045PM', 'city': 'Rotterdam', 'country': 'Netherlands', 'facility': 'Franciscus Gasthuis en Vlietland', 'geoPoint': {'lat': 51.9225, 'lon': 4.47917}}, {'zip': '3079DZ', 'city': 'Rotterdam', 'country': 'Netherlands', 'facility': 'Maasstad ziekenhuis', 'geoPoint': {'lat': 51.9225, 'lon': 4.47917}}, {'zip': '5022GC', 'city': 'Tilburg', 'country': 'Netherlands', 'facility': 'Elisabeth-TweeSteden Ziekenhuis', 'geoPoint': {'lat': 51.55551, 'lon': 5.0913}}, {'zip': '5400AS', 'city': 'Uden', 'country': 'Netherlands', 'facility': 'Bernhoven Ziekenhuis', 'geoPoint': {'lat': 51.66083, 'lon': 5.61944}}, {'zip': '5504DB', 'city': 'Veldhoven', 'country': 'Netherlands', 'facility': 'Máxima Medisch Centrum', 'geoPoint': {'lat': 51.41833, 'lon': 5.40278}}, {'city': 'Wolvega', 'country': 'Netherlands', 'facility': 'Nij Barrahus', 'geoPoint': {'lat': 52.87545, 'lon': 5.99691}}], 'overallOfficials': [{'name': 'Annemiek Nap, Prof.dr.', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Gynecologist, head of department of Obstetrics and Gynaecology'}, {'name': 'Annemiek Nap, Prof MD PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Gynecologist, head of department of Obstetrics and Gynecology'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Radboud University Medical Center', 'class': 'OTHER'}, 'collaborators': [{'name': 'Goodlife Fertility B.V.', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'SPONSOR'}}}}