SubfertilityNCT01894074
The Effects of an Intensive Lifestyle Intervention on Reproductive Outcomes
A study testing Intensive Dietary Intervention in people with Subfertility and Anovulatory, run by Amy E Rothberg at 1 site in United States.
Trial summary
This is a study to determine whether a low calorie diet using meal replacement shakes compared to current counseling about diet, followed by 3 cycles of clomiphene citrate (if needed) will result in: 1) improvements in ability to ovulate and achieve pregnancy either spontaneously or during 3 clomiphene citrate cycles… Read more about this study
- Who is it for?
- Ages 18 to 35 years, women only
- Conditions the study is for
- Subfertility, Anovulatory, Obese
- What is being tested?
- Intensive Dietary Intervention
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2013to Jul 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Women
- 18 to 35 years old
- Obese(BMI of ≥35≤45 kg/m2)
- Infertility (12 months of unprotected intercourse without conception)
- Ovulatory dysfunction (amenorrhea, irregular cycles, or progesterone level less than 10 ng/mL in the luteal phase)
- Partner with semen analysis demonstrating at least 20 million sperm/mL, 50% motility, and normal morphology by Kruger criteria of 8%
- Evidence of normal uterine anatomy and at least on patent tube documented by hysterosalpingogram or saline infusion sonogram.
- Women with polycystic ovary syndrome
Who cannot join
- Significant heart disease (coronary artery disease, Class II-VI Heart Failure, arrythmia)
- Chronic Kidney Disease, Stage IV or greater
- Significant gastrointestinal tract diseases (e.g. IBD)
- Autoimmune disorders (e.g. systemic lupus erythematosus)
- Neurological (e.g. Multiple Sclerosis)
- Psychiatric disorders (Bipolar, Major Depression)
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- History of or current eating disorders or substance abuse
- Endocrine disorders (Type 1 diabetes, adrenal, pituitary or uncontrolled thyroid disease)
- HIV/AIDS
- Significant anemia
- History of or current clotting disorder
- Cancer other than minor skin cancers
- Other conditions that would complicated pregnancy.
- Women will be excluded if they are taking anti-obesity drugs, or appetite suppressants within the last 2 months, or have had previous bariatric surgery.
- Women will be excluded if they have used hormonal medications within the last 2 months, previous use of ovulation induction medications, have endometriosis by American Fertility Society (AFS) class III or IV, have an FSH > 10 IU/mL or couples using donor sperm or are already pregnant.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effects of an Intensive Lifestyle Intervention on Reproductive Outcomes in Obese, Subfertile Women
This is a study to determine whether a low calorie diet using meal replacement shakes compared to current counseling about diet, followed by 3 cycles of clomiphene citrate (if needed) will result in: 1) improvements in ability to ovulate and achieve pregnancy either spontaneously or during 3 clomiphene citrate cycles 2) greater weight loss with reductions in waist and hip circumferences and improvements in hormones that are involved in allowing pregnancy to occur and hormones that are involved in metabolism, such as insulin and glucose (sugar) 3) improvements in other health conditions such as blood pressure, and emotional and physical well-being.
Women eligible to participate will be between the ages of 18-35 with a BMI (ratio of weight in kg divided by height in m2) of ≥ 35≤45 kg/m2 who are seeking help for anovulatory infertility including women with a diagnosis of polycystic ovarian syndrome (PCOS).
Read the detailed description
More than 33% of U.S. adults over the age of 20 are obese (BMI ≥30 kg/m2), and 6% are severely obese (BMI ≥40 kg/m2). As the prevalence and severity of obesity has increased, so has the number of women who have obesity-related abnormalities in reproductive function, including anovulation and infertility. Specifically, obesity contributes to ovulatory problems and compromises ovarian response to ovulation induction agents such as clomiphene.
Women seeking assistance from specialists for reproductive concerns are both anxious to achieve pregnancy and highly motivated. We propose to assess the relative efficacy of very low energy diet (VLED) using liquid meal replacement vs. standard of care dietary counseling and education (DCE) on the metabolic effects of weight reduction in the obese, subfertile population and assess ovulation and time to conception in these women. We hypothesize that use of a very low energy diet with resultant rapid and profound weight loss and marked improvement in metabolic state, will increase the rate of spontaneous cycling, improve unassisted and clomiphene-assisted ovulation and significantly improve conception and pregnancy rates. Because of the direct relationship between obesity and anovulation, we will test whether evaluation of both habitual dietary intake and plasma metabolomic profiles can be used to identify specific dietary components and metabolites that predict successful or unsuccessful induction of ovulation and pregnancy in response to weight loss with or without clomiphene citrate.
32 reproductive age women with a BMI ≥35≤45 kg/m2 will be randomized to 12 weeks of VLED or DCE and ovulation rates and time to conception between groups will be assessed over a 6 month period. We will also evaluate between group differences in rate of weight loss, absolute weight lost, BMI, waist and hip circumferences as well as reproductive and metabolic hormone levels. Luteinizing hormone (LH), follicle stimulating hormone (FSH), androgens, leptin, glucose and insulin (HOMA), and β-cell function (Matsuda Index).
We will assess if clinical, hormonal, dietary or metabolomic profiles, can predict response to weight loss or clomiphene citrate in improving ovulation. Women will be assessed for clinical and molecular phenotypes, including plasma metabolomic profiles. Metabolomic profiles will be adjusted for chronic dietary intake. An initial assessment of the levels of dietary components, metabolites or metabolic pathways that predict response will be investigated.
We will determine program acceptability and differences in the change in co-morbid health conditions, quality-of-life, and psychological well-being in standard of care and VLED-based weight loss participants. Important physiological benefits arise from weight loss and the magnitude of these changes will be assessed in the group of patients seeking reproductive assistance.
This pilot study will provide the first information on the relative success of aggressive, short-term weight loss in the treatment of infertility as defined by improvement in ovulation and conception and provide data for larger, definitive trials of this approach. The study will allow assessment of the feasibility and acceptability of translating VLED treatment-based clinical care and research developed by the University of Michigan Investigational Weight Management Clinic to a specialized population seeking reproductive assistance. Finally, this study will provide important preliminary data for a larger trial to assess the health effects on the mother and the offspring as a result of aggressive intervention to alter the pre-pregnancy metabolic environment in reproductive age women.
- Conditions
- Subfertility, Anovulatory, Obese
- Being tested
- Intensive Dietary Intervention, Placebo
- Keywords
- Subfertility, Anovulatory, Obese, Women
- Medical subject headings
- Infertility, Anovulation, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intensive Dietary InterventionBehavioural
Also called Very low energy diet
Intensive dietary intervention of 800 kcal/day using liquid meal replacement for a total of 12 weeks to reduce weight to 15% from baseline weight.
PlaceboBehavioural
Also called Lifestyle counseling
Lifestyle counseling: standard dietary education and counseling with a goal of reducing to 1500-1800 kcal/day
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Lifestyle counseling:standard dietary education and counseling with a goal of reducing calories to 1500-1800 kcal/day Receives: Behavioral: Placebo |
| Intensive Dietary Intervention | Active comparator | Intensive Dietary Intervention employing very low energy diet (800 kcal/day) x 12 weeks followed by transition to regular foodstuffs over 4-6 weeks. Receives: Behavioral: Intensive Dietary Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in ovulatory cycling
The rate of spontaneous cycling (detected by LH surge) or evidence of menses. Improvement in either unassisted and clomiphene-assisted ovulation (for up to and including 3 cycles of clomiphene citrate)
Measured: 24 months
Secondary outcomes (1)
Metabolic State
Improvement in weight, BMI, waist circumference, hip circumference Improvement in co-morbid health conditions as measured by HbA1C, fasting plasma glucose, total cholesterol profile, HDL, non-HDL and LDL cholesterol levels, glucose and insulin levels (measured during 2 hour oral glucose tolerance testing), leptin, estradiol, LH, FSH, total testosterone levels Changes in molecular phenotype in response to change in dietary nutrients as measured by metabolomic profiling
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2013 (estimated)
- Study startJul 2013
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for SubfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amy E Rothberg
- Sponsor type
- University, hospital or other
- Collaborators
- University of Michigan
- Responsible party
- Sponsor-investigator, Amy E Rothberg, University of Michigan
- Investigators
- Amy E Rothberg, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01894074
- Sponsor's protocol ID
- HUM00068360
- Status last verified
- Dec 2015
- First submitted
- 2 Jul 2013
- Last updated
- 4 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Clark AM, Thornley B, Tomlinson L, Galletley C, Norman RJ. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod. 1998 Jun;13(6):1502-5. doi: 10.1093/humrep/13.6.1502.
PubMed 9688382Rothberg A, Lanham M, Randolph J, Fowler C, Miller N, Smith Y. Feasibility of a brief, intensive weight loss intervention to improve reproductive outcomes in obese, subfertile women: a pilot study. Fertil Steril. 2016 Oct;106(5):1212-1220. doi: 10.1016/j.fertnstert.2016.06.004. Epub 2016 Jun 20.
PubMed 27336206
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of an Intensive Lifestyle Intervention on Reproductive Outcomes in Obese, Subfertile Women
- ClinicalTrials.gov ID
- NCT01894074
- Acronym / sponsor ID
- HUM00068360
- Conditions
- Subfertility, Anovulatory, Obese
- Keywords
- Subfertility, Anovulatory, Obese, Women
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Amy E RothbergUniversity, hospital or other
- Collaborators
- University of Michigan
- Study start
- Jul 2013
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 9 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a study to determine whether a low calorie diet using meal replacement shakes compared to current counseling about diet, followed by 3 cycles of clomiphene citrate (if needed) will result in: 1) improvements in ability to ovulate and achieve pregnancy either spontaneously or during 3 clomiphene citrate cycles 2) greater weight loss with reductions in waist and hip circumferences and improvements in hormones that are involved in allowing pregnancy to occur and hormones that are involved in metabolism, such as insulin and glucose (sugar) 3) improvements in other health conditions such as blood pressure, and emotional and physical well-being.
Women eligible to participate will be between the ages of 18-35 with a BMI (ratio of weight in kg divided by height in m2) of ≥ 35≤45 kg/m2 who are seeking help for anovulatory infertility including women with a diagnosis of polycystic ovarian syndrome (PCOS).
Detailed description
More than 33% of U.S. adults over the age of 20 are obese (BMI ≥30 kg/m2), and 6% are severely obese (BMI ≥40 kg/m2). As the prevalence and severity of obesity has increased, so has the number of women who have obesity-related abnormalities in reproductive function, including anovulation and infertility. Specifically, obesity contributes to ovulatory problems and compromises ovarian response to ovulation induction agents such as clomiphene.
Women seeking assistance from specialists for reproductive concerns are both anxious to achieve pregnancy and highly motivated. We propose to assess the relative efficacy of very low energy diet (VLED) using liquid meal replacement vs. standard of care dietary counseling and education (DCE) on the metabolic effects of weight reduction in the obese, subfertile population and assess ovulation and time to conception in these women. We hypothesize that use of a very low energy diet with resultant rapid and profound weight loss and marked improvement in metabolic state, will increase the rate of spontaneous cycling, improve unassisted and clomiphene-assisted ovulation and significantly improve conception and pregnancy rates. Because of the direct relationship between obesity and anovulation, we will test whether evaluation of both habitual dietary intake and plasma metabolomic profiles can be used to identify specific dietary components and metabolites that predict successful or unsuccessful induction of ovulation and pregnancy in response to weight loss with or without clomiphene citrate.
32 reproductive age women with a BMI ≥35≤45 kg/m2 will be randomized to 12 weeks of VLED or DCE and ovulation rates and time to conception between groups will be assessed over a 6 month period. We will also evaluate between group differences in rate of weight loss, absolute weight lost, BMI, waist and hip circumferences as well as reproductive and metabolic hormone levels. Luteinizing hormone (LH), follicle stimulating hormone (FSH), androgens, leptin, glucose and insulin (HOMA), and β-cell function (Matsuda Index).
We will assess if clinical, hormonal, dietary or metabolomic profiles, can predict response to weight loss or clomiphene citrate in improving ovulation. Women will be assessed for clinical and molecular phenotypes, including plasma metabolomic profiles. Metabolomic profiles will be adjusted for chronic dietary intake. An initial assessment of the levels of dietary components, metabolites or metabolic pathways that predict response will be investigated.
We will determine program acceptability and differences in the change in co-morbid health conditions, quality-of-life, and psychological well-being in standard of care and VLED-based weight loss participants. Important physiological benefits arise from weight loss and the magnitude of these changes will be assessed in the group of patients seeking reproductive assistance.
This pilot study will provide the first information on the relative success of aggressive, short-term weight loss in the treatment of infertility as defined by improvement in ovulation and conception and provide data for larger, definitive trials of this approach. The study will allow assessment of the feasibility and acceptability of translating VLED treatment-based clinical care and research developed by the University of Michigan Investigational Weight Management Clinic to a specialized population seeking reproductive assistance. Finally, this study will provide important preliminary data for a larger trial to assess the health effects on the mother and the offspring as a result of aggressive intervention to alter the pre-pregnancy metabolic environment in reproductive age women.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Behavioral: PlaceboLifestyle counseling:standard dietary education and counseling with a goal of reducing calories to 1500-1800 kcal/day |
| Intensive Dietary Intervention | Active comparator | Behavioral: Intensive Dietary InterventionIntensive Dietary Intervention employing very low energy diet (800 kcal/day) x 12 weeks followed by transition to regular foodstuffs over 4-6 weeks. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Women
- 18 to 35 years old
- Obese(BMI of ≥35≤45 kg/m2)
- Infertility (12 months of unprotected intercourse without conception)
- Ovulatory dysfunction (amenorrhea, irregular cycles, or progesterone level less than 10 ng/mL in the luteal phase)
Key exclusion criteria (15 listed)
- Significant heart disease (coronary artery disease, Class II-VI Heart Failure, arrythmia)
- Chronic Kidney Disease, Stage IV or greater
- Significant gastrointestinal tract diseases (e.g. IBD)
- Autoimmune disorders (e.g. systemic lupus erythematosus)
- Neurological (e.g. Multiple Sclerosis)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intensive Dietary InterventionAlso: Very low energy dietIntensive dietary intervention of 800 kcal/day using liquid meal replacement for a total of 12 weeks to reduce weight to 15% from baseline weight. | Behavioural | Intensive Dietary Intervention |
| PlaceboAlso: Lifestyle counselingLifestyle counseling: standard dietary education and counseling with a goal of reducing to 1500-1800 kcal/day | Behavioural | Placebo |
Primary outcome
Improvement in ovulatory cycling
Time frame: 24 months
The rate of spontaneous cycling (detected by LH surge) or evidence of menses. Improvement in either unassisted and clomiphene-assisted ovulation (for up to and including 3 cycles of clomiphene citrate)
1 secondary outcome
Metabolic State
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2015.
- Background: PubMed 9688382Clark AM, Thornley B, Tomlinson L, Galletley C, Norman RJ. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod. 1998 Jun;13(6):1502-5. doi: 10.1093/humrep/13.6.1502.
- Derived from this study: PubMed 27336206Rothberg A, Lanham M, Randolph J, Fowler C, Miller N, Smith Y. Feasibility of a brief, intensive weight loss intervention to improve reproductive outcomes in obese, subfertile women: a pilot study. Fertil Steril. 2016 Oct;106(5):1212-1220. doi: 10.1016/j.fertnstert.2016.06.004. Epub 2016 Jun 20.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amy E Rothberg, MD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intensive Dietary Intervention in people with Subfertility and Anovulatory, run by Amy E Rothberg at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in ovulatory cycling (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01894074, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2015.